Progressive osseous heteroplasia (POH) is a rare genetic bone disorder characterized clinically by progressive extraskeletal bone formation presenting in early life with cutaneous ossification, that progressively involves subcutaneous and then subsequently deep connective tissues, including muscle and fascia. POH overlaps with a number of related genetic disorders including Albright hereditary osteodystrophy, pseudohypoparathyroidism (see these terms), and primary osteoma cutis, that share the common features of superficial heterotopic ossification in association with inactivating mutations of GNAS gene (20q13.2-q13.3), coding for guanine nucleotide-binding proteins. POH can, however, be distinguished clinically by the deep and progressive nature of the heterotopic bone formation.
Progressive osseous heteroplasia (POH) is a progressive bone disorder in which bone forms (ossifies) within skin and muscle tissue. It usually becomes apparent in infancy with skin (cutaneous) ossification, which progresses to involvement of subcutaneous and deep tissues, including muscle. In some cases, it first becomes apparent later in childhood or in early adulthood. Ossification may cause pain and open sores (ulcers) in affected areas of the body. Joints may become involved over time, causing impaired mobility. POH is caused by a mutation in the GNAS gene and is inherited in an autosomal dominant manner.
Osteoma cutis Other names POH [1] Perforating osteoma cutis, skin of the foot Specialty Oncology , dermatology Osteoma cutis is a cutaneous condition characterized by the presence of bone within the skin in the absence of a preexisting or associated lesion. [2] : 529 See also [ edit ] Calcinosis cutis Skin lesion List of cutaneous conditions References [ edit ] ^ "OMIM Entry - # 166350 - OSSEOUS HETEROPLASIA, PROGRESSIVE; POH" . omim.org . Retrieved 18 April 2019 . ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology . Saunders Elsevier. ISBN 978-0-7216-2921-6 . External links [ edit ] Classification D ICD - 10 : D23 ( ILDS D23.L79) OMIM : 166350 External resources eMedicine : article/1103575 Orphanet : 2762 This cutaneous condition article is a stub . You can help Wikipedia by expanding it . v t e
McKusick (1989) observed osteoma cutis in a 38-year-old man who also had unerupted teeth, severe bilateral carpal tunnel syndrome, and unusual changes in the bones of the forearms and legs that were quite different from those of pseudohypoparathyroidism. ... Based on clinical criteria, they concluded that POH and progressive HO syndromes are at the severe end of a phenotypic spectrum of GNAS-inactivating conditions associated with extraskeletal ossification and that they can be distinguished from other GNAS-based disorders by a single clinical parameter, i.e., the extension of HO from superficial to deep tissue.
Progressive osseous heteroplasia is a disorder in which bone forms within skin and muscle tissue. Bone that forms outside the skeleton is called heterotopic or ectopic bone. In progressive osseous heteroplasia, ectopic bone formation begins in the deep layers of the skin (dermis and subcutaneous fat) and gradually moves into other tissues such as skeletal muscle and tendons. The bony lesions within the skin may be painful and may develop into open sores (ulcers). Over time, joints can become involved, resulting in impaired mobility.
Cronkhite-Canada syndrome (CCS) is a rare gastrointestinal (GI) polyposis syndrome characterized by the association of non-hereditary GI polyposis with the cutaneous triad of alopecia, nail changes and hyperpigmentation. ... Differential diagnosis Differential diagnosis includes familial adenomatous polyposis, hyperplastic polyposis syndrome, cap polyposis, juvenile polyposis syndrome, Peutz-Jeghers syndrome and Cowdensyndrome (see these terms), as well as lipomatous polyposis, inflammatory polyposis and lymphomatous polyposis.
Cronkhite–Canada syndrome Other names Gastrointestinal polyposis-skin pigmentation-alopecia-fingernail changes syndrome Cronkhite–Canada syndrome affects the digestive tract Specialty Gastroenterology Cronkhite–Canada syndrome is a rare syndrome characterized by multiple polyps of the digestive tract . ... Recent findings have called this hypothesis into question; specifically, the hair and nail changes may not improve with improved nutrition. [ citation needed ] Other conditions consisting of multiple hamartomatous polyps of the digestive tract include Peutz–Jeghers syndrome , juvenile polyposis , and Cowden disease . Related polyposis conditions are familial adenomatous polyposis , attenuated familial adenomatous polyposis , Birt–Hogg–Dubé syndrome and MUTYH . [ citation needed ] Diagnosis [ edit ] There is no specific test to diagnose Cronkhite–Canada syndrome. ... "Generalized gastrointestinal polyposis; an unusual syndrome of polyposis, pigmentation, alopecia and onychotrophia". ... PMID 12868681 . ^ "Cronkhite-Canada Syndrome" . NORD (National Organization for Rare Disorders) .
Cronkhite-Canada syndrome is a rare gastrointestinal disorder characterized by widespread colon polyps , unhealthy looking (dystrophic) nails, hair loss ( alopecia ), darkening skin (such as on the hands, arms, neck and face), diarrhea, weight loss, stomach pain, and/or excess fluid accumulation in arms and legs (peripheral edema).
Description Cronkhite-Canada syndrome is characterized by gastrointestinal hamartomatous polyposis, alopecia, onychodystrophy, skin hyperpigmentation, and diarrhea. ... Clinical Features Cronkhite and Canada (1955) described 2 unrelated patients with a syndrome of gastrointestinal polyposis, skin hyperpigmentation, alopecia, onychodystrophy, and diarrhea. ... The pigmentation is diffuse rather than spotted as in the Peutz-Jeghers syndrome (175200). Sweetser et al. (2012) described 14 consecutive cases of Cronkhite-Canada syndrome seen at the Mayo Clinic on whom tissue and follow-up were available. ... Inheritance Sweetser et al. (2012) stated that 'Cronkhite-Canada syndrome...is a noninherited condition.'
A rare genetic disease characterized as an inherited skin tumour predisposition syndrome presenting with skin appendage tumours, namely cylindromas, spiradenomas and trichoepitheliomas Epidemiology To date, more than 200 cases of CYLD Cutaneous Syndrome (CCS) have been reported in the literature. ... Differential diagnosis Differential clinical diagnosis for multiple skin and/or scalp tumours include Birt-Hogg-Dubé syndrome, neurofibromatosis type 1, Cowdensyndrome, tuberous sclerosis complex, Marie-Unna hypotrichosis, basal cell naevus syndrome, pilar cysts, multiple syringomas.
CYLD cutaneous syndrome causes the growth of several types of non-cancerous (benign) skin tumors. ... The types of tumors that occur in CYLD cutaneous syndrome may include cylindromas , spiradenomas , and trichoepitheliomas . ... Other complications may include an increased risk to develop basal cell cancer of the salivary gland or deafness due to the growth of a tumor in the ear canal. CYLD cutaneous syndrome is caused by genetic variants in the CYLD gene and is inherited in an autosomal dominant pattern. Diagnosis of CYLD cutaneous syndrome is based on the symptoms, clinical exam, and microscopic exam of the tumor tissue. ... The conditions known as Brooke-Spiegler syndrome, familial cylindromatosis, and multiple familial trichoepithelioma are now recognized to be part of CYLD cutaneous syndrome.
CYLD cutaneous syndrome is a genetic condition characterized by the growth of multiple noncancerous (benign) skin tumors. ... While the skin tumors associated with CYLD cutaneous syndrome are typically benign, occasionally they may become cancerous (malignant). ... For reasons that are unclear, females with CYLD cutaneous syndrome tend to develop more tumors than males with this condition. ... CYLD cutaneous syndrome includes the conditions previously called Brooke-Spiegler syndrome, multiple familial trichoepithelioma, and familial cylindromatosis. ... Frequency The prevalence of CYLD cutaneous syndrome is unknown, but the condition is estimated to affect more than 1 in 100,000 individuals.
A number sign (#) is used with this entry because Brooke-Spiegler syndrome (BRSS) is caused by heterozygous mutation in the CYLD gene (605018) on chromosome 16q12. ... Blake and Toro (2009) provided a review of Brooke-Spiegler syndrome and pathogenic mutations in the CYLD gene. ... Weyers et al. (1993) reported a patient with Brooke-Spiegler syndrome in whom spiradenomas were found in the immediate vicinity of trichoepitheliomas and in continuity with follicles. ... Nasti et al. (2009) reported an Italian mother and son with variable manifestations of Brooke-Spiegler syndrome. The 79-year-old mother began developing skin lesions at age 16. ... History Weyers et al. (1993) noted that Brooke-Spiegler syndrome is named eponymically after the 2 physicians who first reported these neoplasms, Henry G.
Proteus syndrome is a rare condition characterized by overgrowth of the bones, skin, and other tissues. ... Pulmonary embolism is a common cause of death in people with Proteus syndrome. Frequency Proteus syndrome is a rare condition with an incidence of less than 1 in 1 million people worldwide. ... Researchers believe that Proteus syndrome may be overdiagnosed, as some individuals with other conditions featuring asymmetric overgrowth have been mistakenly diagnosed with Proteus syndrome. ... Instead, these individuals actually have condition that is considered part of a larger group of disorders called PTEN hamartoma tumor syndrome. One name that has been proposed for the condition is segmental overgrowth, lipomatosis, arteriovenous malformations, and epidermal nevus (SOLAMEN) syndrome; another is type 2 segmental Cowdensyndrome. However, some scientific articles still refer to PTEN -related Proteus syndrome. Learn more about the gene associated with Proteus syndrome AKT1 Inheritance Pattern Because Proteus syndrome is caused by AKT1 gene mutations that occur during early development, the disorder is not inherited and does not run in families.
Summary Clinical characteristics. Proteus syndrome is characterized by progressive segmental or patchy overgrowth most commonly affecting the skeleton, skin, adipose, and central nervous systems. ... Diagnosis Suggestive Findings Proteus syndrome (PS) should be suspected in a proband with the following. ... Clinical Characteristics Clinical Description Proteus syndrome (PS) displays a wide range of severity. ... A phenotypic subtype, described as type II segmental Cowdensyndrome [Happle 2007] or SOLAMEN syndrome [Caux et al 2007], is the consequence of a germline pathogenic variant in PTEN with a somatic, mosaic second PTEN variant that gives the phenotype its segmental attributes. ... Klippel-Trenaunay syndrome is a disorder that manifests both overgrowth and vascular malformations.
Cohen (2014) provided a detailed review of the clinical features, diagnosis, and management issues of Proteus syndrome. Some authors (Zhou et al. (2000, 2001); Smith et al., 2002) have reported a 'Proteus-like' syndrome associated with germline and tissue-specific somatic mutations in the PTEN gene (601728), which is mutated in Cowdensyndrome (CWS1); see 158350 for a discussion of these patients. ... The disorder might be confused with the Klippel-Trenaunay-Weber syndrome (149000) and with Ollier disease (166000) and Maffucci syndrome (614569). ... Some similarities to the Bannayan-Zonana syndrome (see 153480) and linear sebaceous nevus syndrome (163200) were noted. ... He suggested this mechanism also for Schimmelpenning-Feuerstein-Mims syndrome (163200) and the McCune-Albright syndrome (174800). ... See encephalocraniocutaneous lipomatosis (ECCL; 613001), which shares many features with Proteus syndrome. Elattoproteus Syndrome Happle (1999) suggested the designation elattoproteus syndrome for a disorder that he considered to be an inverse form of Proteus syndrome.
Proteus syndrome (PS) is a very rare and complex hamartomatous overgrowth disorder characterized by progressive overgrowth of the skeleton, skin, adipose, and central nervous systems. ... Etiology Causal mutations of PS have been reported in two components of the phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway: PTEN , which make PS a part of the PTEN Hamartoma Tumor Syndrome (PTHS; see this term) and AKT1 . ... If these criteria are not met then a patient may be diagnosed with Proteus-like syndrome (see this term). Molecular genetic testing may confirm diagnosis. Differential diagnosis Differential diagnoses include Klippel-Trenaunay-Weber syndrome, hemihypertrophy, Ollier disease, macrodactyly, Maffucci syndrome, CLOVE syndrome, neurofibromatosis type 1 and other PHTS disorders (see these terms).
Proteus syndrome is characterized by excessive growth of a part or portion of the body. The overgrowth is usually asymmetric, which means it affects the right and left sides of the body differently. Newborns with Proteus syndrome have few or no signs of the disorder. ... It may result in differences in appearance and with time, an increased risk for blood clots and tumors. Some people with Proteus syndrome have neurological abnormalities, including intellectual disability, seizures, and vision loss, as well as distinctive facial features. Proteus syndrome is caused by a change (mutation) in the AKT1 gene. ... This is why only a portion of the body is affected and why individuals with Proteus syndrome can be very differently affected.
A number sign (#) is used with this entry because of evidence that metachondromatosis (METCDS) is caused by heterozygous mutation in the PTPN11 gene (176876) on chromosome 12q24. Description Metachondromatosis is characterized by exostoses (osteochondromas), commonly of the hands and feet, and enchondromas of long bone metaphyses and iliac crests (summary by Sobreira et al., 2010). Clinical Features Maroteaux (1971) described 2 families with skeletal radiologic features of both multiple exostoses (133700) and Ollier disease (166000). He called the disorder metachondromatosis and suggested autosomal dominant inheritance on the basis of 1 family with 5 affected persons. Lachman et al. (1974) reported a case. Kennedy (1983) presented the case of a 9.5-year-old boy in whom 'bumps' on the hands, feet and knees had been noted at age 5.
Other diseases to be considered include the non-hereditary conditions Ollier disease and Maffucci syndrome (in which multiple enchondromas are found in the medulla of the bone and are predominantly unilateral), and dysplasia epiphysealis hemimelica (DEH; characterized by a cartilaginous overgrowth mainly located in the lower extremities on one side of the body) (see these terms).
Metachondromatosis (MC) is a rare bone disorder characterized by the presence of both multiple enchondromas and osteochondroma -like lesions. The first signs occur during the first decade of life. Osteochondromas most commonly occur in the hands and feet (predominantly in digits and toes), and enchondromas involve the iliac crests and metaphyses of long bones. The lesions typically spontaneously decrease in size or regress. Nerve paralysis or vascular complications may occur in some cases. The condition has been linked to mutations in the PTPN11 gene in several families and is inherited in an autosomal dominant manner. Treatment may include surgery to remove osteochondromas in severe cases.[8171]
Insulinomas can produce large amounts of insulin, causing hypoglycemia . [8] [9] Pituitary adenomas can cause elevated levels of hormones such as growth hormone and insulin-like growth factor-1 , which cause acromegaly ; prolactin ; ACTH and cortisol , which cause Cushings disease ; TSH , which causes hyperthyroidism ; and FSH and LH . [10] Bowel intussusception can occur with various benign colonic tumors. [11] Cosmetic effects can be caused by tumors, especially those of the skin, possibly causing psychological or social discomfort for the person with the tumor. [12] Vascular tissue tumors can bleed, in some cases leading to anemia . [13] Causes [ edit ] PTEN hamartoma syndrome [ edit ] PTEN hamartoma syndrome consists of four distinct hamartomatous disorders characterised by genetic mutations in the PTEN gene; Cowdensyndrome , Bannayan-Riley-Ruvalcaba syndrome , Proteus syndrome and Proteus-like syndrome . ... Absent or dysfunctional PTEN protein allows cells to over-proliferate, causing hamartomas. [14] Other syndromes [ edit ] Cowdensyndrome is an autosomal dominant genetic disorder characterised by multiple benign hamartomas ( trichilemmomas and mucocutaneous papillomatous papules) as well as a predisposition for cancers of multiple organs including the breast and thyroid. [15] [16] Bannayan-Riley-Ruvalcaba syndrome is a congenital disorder characterised by hamartomatous intestinal polyposis, macrocephaly , lipomatosis , hemangiomatosis and glans penis macules. [14] [17] Proteus syndrome is characterised by nevi , asymmetric overgrowth of various body parts, adipose tissue dysregulation, cystadenomas , adenomas , vascular malformation. [18] [19] Endoscopic image of sigmoid colon of a patient with familial adenomatous polyposis . ... PMID 19668082 . ^ Pilarski R, Eng C (May 2004). "Will the real Cowdensyndrome please stand up (again)? ... PMID 15121767 . ^ Eng C (November 2000). "Will the real Cowdensyndrome please stand up: revised diagnostic criteria" . ... PMID 11073535 . ^ Eng C (September 2003). "PTEN: one gene, many syndromes". Hum. Mutat . 22 (3): 183–98. doi : 10.1002/humu.10257 .
A number sign (#) is used with this entry because of evidence that juvenile primary lateral sclerosis (PLSJ) is caused by homozygous mutation in the gene encoding alsin (ALS2; 606352) on chromosome 2q33. Juvenile amyotrophic lateral sclerosis-2 (205100) and infantile-onset ascending spastic paralysis (IAHSP; 607225) are allelic disorders with overlapping phenotypes. See also adult-onset PLS (611637), which occurs sporadically or shows autosomal dominant inheritance. Description Although primary lateral sclerosis is similar to amyotrophic lateral sclerosis (ALS; 105400), they are considered to be clinically distinct progressive paralytic neurodegenerative disorders. Following a period of diagnostic confusion, the clinical distinction between ALS and PLS became clear and diagnostic criteria established (Pringle et al., 1992).
A very rare motor neuron disease characterized by progressive upper motor neuron dysfunction leading to loss of the ability to walk with wheelchair dependence, and subsequently, loss of motor speech production. Epidemiology The prevalence and incidence of JPLS are not known. A very small number of cases have been reported to date with this condition. The disorder has been described in various ethnic groups. Clinical description Affected patients are usually normal at birth and have normal early development. During the second year of life, they lose the ability to walk (some patients never walk due to early severe spasticity) and then develop slowly progressive upper motor neuron disorders including pseudobulbar palsy and spastic quadriplegia. Other signs include clumsiness, muscle weakness and balance difficulties.
Juvenile primary lateral sclerosis is a rare disorder characterized by progressive weakness and stiffness of muscles in the arms, legs, and face. This disorder damages motor neurons, which are specialized nerve cells in the brain and spinal cord that control muscle movement. Symptoms begin in early childhood and progress over a period of 15 to 20 years. Juvenile primary lateral sclerosis is caused by mutations in the ALS2 gene. It is inherited in an autosomal recessive pattern.
Juvenile primary lateral sclerosis is a rare disorder characterized by progressive weakness and tightness (spasticity) of muscles in the arms, legs, and face. The features of this disorder are caused by damage to motor neurons, which are specialized nerve cells in the brain and spinal cord that control muscle movement. Symptoms of juvenile primary lateral sclerosis begin in early childhood and progress slowly over many years. Early symptoms include clumsiness, muscle weakness and spasticity in the legs, and difficulty with balance. As symptoms progress, the spasticity spreads to the arms and hands and individuals develop slurred speech, drooling, difficulty swallowing, and an inability to walk.
Genetic counseling. Marinesco-Sjögren syndrome (MSS) is inherited in an autosomal recessive manner. ... Diagnosis Suggestive Findings Marinesco-Sjögren syndrome (MSS) should be suspected in individuals with the following clinical findings: Cerebellar ataxia with cerebellar atrophy, dysarthria, and nystagmus MRI. ... Clinical Characteristics Clinical Description Infants with Marinesco-Sjögren syndrome (MSS) are born after uncomplicated pregnancies. ... Nomenclature Previously used terms for Marinesco-Sjögren syndrome: Garland-Moorhouse syndrome Marinesco-Garland syndrome Hereditary oligophrenic cerebello-lental degeneration Individuals first described as having Marinesco-Sjögren-like syndrome (also called ataxia-juvenile cataract-myopathy-intellectual disability [OMIM 248810]) were later found to have classic MSS with SIL1 pathogenic variants, resulting in discontinuation of this OMIM entry. ... Differential Diagnosis In individuals with atypical features of Marinesco-Sjögren syndrome (MSS), the differential diagnostic possibilities that should be considered are listed in Table 2.
Marinesco-Sjögren syndrome is a condition that has a variety of signs and symptoms affecting many tissues. People with Marinesco-Sjögren syndrome have clouding of the lens of the eyes (cataracts ) that usually develops soon after birth or in early childhood. ... Most people with Marinesco-Sjögren syndrome have mild to moderate intellectual disability. ... As a result, puberty is either delayed or absent. Frequency Marinesco-Sjögren syndrome appears to be a rare condition. ... This accumulation likely damages and destroys cells in many different tissues, leading to ataxia, myopathy, and the other features of Marinesco-Sjögren syndrome. Approximately one-third of people with Marinesco-Sjögren syndrome do not have identified mutations in the SIL1 gene.
Marinesco-Sjögren syndrome (MSS) belongs to the group of autosomal recessive cerebellar ataxias. ... Etiology It has been suggested that the MSS with myoglobinuria and congenital cataracts-facial dysmorphism-neuropathy (CCFDN) syndromes are genetically identical as they both map to chromosome 18qter.
A number sign (#) is used with this entry because Marinesco-Sjogren syndrome (MSS) is caused by homozygous or compound heterozygous mutation in the SIL1 gene (608005) on chromosome 5q31. ... Skre and Berg (1977) observed 10 persons with Marinesco-Sjogren syndrome in 2 kindreds, 9 of whom also had hypogonadism. ... In 4 members of 2 Finnish families, Herva et al. (1987) described a cerebrooculomuscular syndrome that the authors considered to be distinct from MSS. ... Senderek et al. (2005) defined Marinesco-Sjogren syndrome as a disease of endoplasmic reticulum dysfunction and suggested that this organelle has a role in multisystem disorders. ... History Superneau et al. (1985) pointed to a description of this syndrome reported in the Hungarian medical literature in 1904.
A number sign (#) is used with this entry because immunodeficiency-48 (IMD48), characterized by selective T-cell defect (STCD), is caused by homozygous or compound heterozygous mutation in the ZAP70 gene (176947) on chromosome 2q11. Clinical Features Roifman et al. (1989) described a female infant with a novel type of human immunodeficiency characterized by a selective T-cell defect. Peripheral circulating T cells from these patients exclusively expressed CD4, CD3, and T-cell receptor-alpha/beta, but not CD8 molecules on their surface. The inability to produce peripheral CD8 single-positive cells was traced to an intrathymic developmental defect. Whereas CD4(+)/CD8(+)-positive cells were present in the thymic cortex of these patients, only CD4, not CD8, single-positive cells could be detected in the thymic medulla, suggesting a selective block of positive selection of CD8+ cells.
ZAP70 -related severe combined immunodeficiency (SCID) is an inherited disorder that damages the immune system. ZAP70 -related SCID is one of several forms of severe combined immunodeficiency, a group of disorders with several genetic causes. Children with SCID lack virtually all immune protection from bacteria, viruses, and fungi. They are prone to repeated and persistent infections that can be very serious or life-threatening. Often the organisms that cause infection in people with this disorder are described as opportunistic because they ordinarily do not cause illness in healthy people.
A very rare, severe, genetic, combined immunodeficiency disorder characterized by lymphocytosis, decreased peripheral CD8+ T-cells, and presence of normal circulating CD4+ T-cells, leading to immune dysfunction.
A number sign (#) is used with this entry because of evidence that polycystic liver disease-2 with or without kidney cysts (PCLD2) is caused by heterozygous mutation in the SEC63 gene (608648) on chromosome 6q21. Description PCLD2 is an autosomal dominant disease characterized by the presence of multiple liver cysts resulting from structural changes in the biliary tree during development. Abnormal biliary structures may be present early in life, but they usually remain asymptomatic until cyst growth initiates during adulthood. In advanced stages, patients may develop massively enlarged livers, which cause a spectrum of clinical features and complications. Genetic studies suggest that an accumulation of somatic hits in cyst epithelium determines the rate of cyst formation.
A number sign (#) is used with this entry because of evidence that polycystic liver disease-1 with or without kidney cysts (PCLD1) is caused by heterozygous mutation in the PRKCSH gene (177060) on chromosome 19p13. Description Polycystic liver disease-1 is an autosomal dominant condition characterized by the presence of multiple liver cysts of biliary epithelial origin. Although the clinical presentation and histologic features of polycystic liver disease in the presence or absence of autosomal dominant polycystic kidney disease (see, e.g., PKD1, 173900) are indistinguishable, PCLD1 is a genetically distinct form of isolated polycystic liver disease (summary by Reynolds et al., 2000). A subset of patients (28-35%) may develop kidney cysts that are usually incidental findings and do not result in clinically significant renal disease (review by Cnossen and Drenth, 2014). Genetic Heterogeneity of Polycystic Liver Disease See also PCLD2 (617004), caused by mutation in the SEC63 gene (608648) on chromosome 6q21; PCLD3 (617874), caused by mutation in the ALG8 gene (608103) on chromosome 11p; and PCLD4 (617875), causes by mutation in the LRP5 gene (603506) on chromosome 11q13.
Isolated polycystic liver disease (PCLD) is a genetic disorder characterized by the appearance of numerous cysts spread throughout the liver and that in most cases is described as autosomal dominant polycystic liver disease (ADPCLD). Epidemiology The prevalence of ADPCLD is 1/100, 000. Clinical description Women are predominantly affected and have a larger number of cysts than affected males. Cysts are undetectable early in life and usually appear after the age of 40 years. Their number and size increases with age. Symptoms depend on the mass (compression effect) and can include abdominal distension, gastro-esophageal reflux, early satiety, dyspnea, decreased mobility and back pain due to hepatomegaly. Some patients are asymptomatic. Other complications (intracystic hemorrhage or infection, torsion or rupture of cysts) can cause acute abdominal pain.
Polycystic liver disease is an inherited condition characterized by many cysts of various sizes scattered throughout the liver . Abdominal discomfort from swelling of the liver may occur; however, most affected individuals do not have any symptoms. In some cases, polycystic liver disease appears to occur randomly, with no apparent cause. Most cases are inherited in an autosomal dominant fashion. Sometimes, cysts are found in the liver in association with the presence of autosomal dominant polycystic kidney disease (AD-PKD) . In fact, about half of the people who have AD-PKD experience liver cysts.
Diagnosis/testing. The diagnosis of Peutz-Jeghers syndrome is based on clinical findings. ... PTEN hamartoma tumor syndrome (PHTS), an autosomal dominant cancer syndrome caused by mutation of PTEN , includes Cowdensyndrome, Bannayan-Riley-Ruvalcaba syndrome, PTEN -related Proteus syndrome, and a Proteus-like syndrome. The extraintestinal manifestations are more pronounced than intestinal polyposis. The features of Cowdensyndrome that distinguish it from PJS include facial trichilemmomas, mucosal papillomas, acral keratoses, macrocephaly, and tumors of the thyroid, breast, and endometrium. ... Proteus-like syndrome is undefined but refers to individuals with significant clinical features of Proteus syndrome who do not meet the diagnostic criteria for Proteus syndrome. ... = anecdotal association; CC = Carney complex; CHRPE = congenital hypertrophy of the retinal pigment epithelium; CS = Cowdensyndrome; FAP = familial adenomatous polyposis; HNPCC = hereditary non-polyposis colorectal cancer; JPS = juvenile polyposis syndrome The differential diagnosis of oral pigmented lesions includes the following: The Laugier-Hunziker syndrome is characterized by the presence of perioral, digit and nailbed lentiginosis (small, well-demarcated; dark-brown to blue-black in color).
A genetic intestinal polyposis syndrome characterized by development of characteristic hamartomatous polyps throughout the gastrointestinal (GI) tract, and by mucocutaneous pigmentation. This disorder carries a considerably increased risk of GI and extra-GI malignancies. Epidemiology Peutz-Jeghers syndrome (PJS) prevalence estimates range from 1/25,000 to 1/300,000 births. ... Differential diagnosis Differential diagnoses include juvenile polyposis syndrome, hereditary mixed polyposis syndrome, the PTEN hamartoma tumor syndromes, and Carney complex. Antenatal diagnosis Prenatal diagnosis for increased risk pregnancies is available provided that the disease-causing mutation has been identified in the family. Genetic counseling The syndrome is inherited in an autosomal dominant manner.
Peutz-Jeghers syndrome (PJS) is an inherited condition that is associated with an increased risk of growths along the lining of the gastrointestinal tract (called hamartomatous polyps) and certain types of cancer.
Metastases from a malignant polyp in Peutz-Jeghers syndrome was reported by Williams and Knudsen (1965). ... Brigg et al. (1976) observed a case of presumed Peutz-Jeghers syndrome without spots or positive family history. ... Three other reported male patients with Peutz-Jeghers syndrome and gonadal tumors had presented with gynecomastia between birth and 6 years of age. ... Another member developed short bowel syndrome. In the follow-up of 72 patients with PJS in the St. ... In a patient with Peutz-Jeghers syndrome, Markie et al. (1996) demonstrated a pericentric inversion in chromosome 6.
Children with Peutz-Jeghers syndrome often develop small, dark-colored spots on the lips , around and inside the mouth , near the eyes and nostrils, and around the anus. ... In addition, most people with Peutz-Jeghers syndrome develop multiple polyps in the stomach and intestines during childhood or adolescence. ... The resulting uncontrolled cell growth leads to the formation of noncancerous polyps and cancerous tumors in people with Peutz-Jeghers syndrome. A small percentage of people with Peutz-Jeghers syndrome do not have mutations in the STK11 gene. ... Learn more about the gene associated with Peutz-Jeghers syndrome STK11 Inheritance Pattern Peutz-Jeghers syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase the risk of developing noncancerous polyps and cancerous tumors. ... The remaining cases occur in people with no history of Peutz-Jeghers syndrome in their family. These cases appear to result from new (de novo) mutations in the STK11 gene.
Roberts et al. (2006) provided a detailed review of CFC syndrome, including a discussion of the phenotypic overlap of CFC syndrome with Noonan syndrome (NS1; 163950) and Costello syndrome (218040). ... They described mother and daughter who had features consistent with the CFC syndrome but had other features which have been reported in the Noonan syndrome but not in the CFC syndrome, namely, hemorrhagic diathesis and ocular abnormalities. ... Leichtman (1996) described a family suggesting that CFC syndrome is a variable expression of Noonan syndrome. ... Molecular Genetics The phenotypic overlap among CFC syndrome, Noonan syndrome, and Costello syndrome, and the finding of causative mutations for the latter syndromes in the PTPN11 and HRAS (190020) genes, respectively, suggested to Niihori et al. (2006) that the action of the RAS-MAPK pathway is the common underlying mechanism of Noonan syndrome and Costello syndrome and, hence, possibly of CFC syndrome. ... Gripp et al. (2007) reported 13 unrelated patients ages 0 to 8 years with a clinical diagnosis of Costello syndrome (218040), Costello-like syndrome, or thought to have either CFC syndrome or Costello syndrome who were negative for mutations in the HRAS gene.
Cardiofaciocutaneous (CFC) syndrome is a disorder that affects many parts of the body, particularly the heart, face, skin, and hair. People with this condition also have developmental delay and intellectual disability, usually ranging from moderate to severe. The signs and symptoms of CFC syndrome overlap significantly with those of two other conditions, Costello syndrome and Noonan syndrome . These syndromes belong to a group of related conditions called the RASopathies , which are distinguished by their genetic causes and specific pattern of features. It can sometimes be hard to tell these conditions apart in infancy. CFC syndrome is usually caused by a mutation in the BRAF gene, but can also be due to a mutation in the MAP2K1 , MAP2K2 or KRAS g ene.
The face is broader and longer, overall more coarse, than in Noonan syndrome (a clinically similar disorder often confused with CFC syndrome), but usually not as coarse as typically seen in Costello syndrome. ... At present, no longitudinal or natural history studies have been done for CFC syndrome. However, CFC syndrome does have an evolving phenotype. ... By late adolescence to early adulthood, the craniofacial appearance becomes less like that seen in Noonan syndrome. Neoplasias (e.g., benign papillomas or malignancies observed in the other RASopathies including Costello syndrome, Noonan syndrome, or neurofibromatosis type 1) have not been reported in CFC syndrome. ... However, with closer clinical examination, the clinical diagnosis was consistent with CFC syndrome. Costello syndrome and cardiofaciocutaneous (CFC) syndrome have many overlapping phenotypic features, underscoring the difficulty in making a clinical diagnosis based on phenotypic features alone. Individuals with BRAF pathogenic variants have the diagnosis of CFC syndrome, even if they have features that may be present in Costello syndrome or have phenotypic overlap with Noonan syndrome (see following).
Cardiofaciocutaneous syndrome is also characterized by distinctive facial features. ... The signs and symptoms of cardiofaciocutaneous syndrome overlap significantly with those of two other genetic conditions, Costello syndrome and Noonan syndrome. ... Frequency Cardiofaciocutaneous syndrome is a very rare condition whose incidence is unknown. ... In these cases, affected individuals may actually have Costello syndrome or Noonan syndrome, which are also caused by mutations in genes involved in RAS/MAPK signaling. ... The group of related conditions that includes cardiofaciocutaneous syndrome, Costello syndrome, and Noonan syndrome is often called the RASopathies.
A number sign (#) is used with this entry because of evidence that cardiofaciocutaneous syndrome-3 (CFC3) is caused by heterozygous mutation in the MAP2K1 gene (176872) on chromosome 15q22. For a general phenotypic description and a discussion of genetic heterogeneity of cardiofaciocutaneous syndrome, see CFC1 (115150). Description Cardiofaciocutaneous syndrome (CFC) is a complex developmental disorder involving characteristic craniofacial features, cardiac anomalies, hair and skin abnormalities, postnatal growth deficiency, hypotonia, and developmental delay.
A number sign (#) is used with this entry because this form of cardiofaciocutaneous syndrome (CFC2) is caused by heterozygous mutation in the KRAS gene (190070) on chromosome 12p12.1. For a general phenotypic description and a discussion of genetic heterogeneity of cardiofaciocutaneous syndrome, see CFC1 (115150). Description Cardiofaciocutaneous (CFC) syndrome is a multiple congenital anomaly disorder characterized by a distinctive facial appearance, heart defects, and mental retardation (summary by Niihori et al., 2006). ... Clinical Features Wieczorek et al. (1997) described a female patient (patient 2) with cardiofaciocutaneous syndrome. She was noted to be hypotonic in the first few weeks of life, and early development was complicated by hypertrophic obstructive cardiomyopathy, atrial septal defect, and pulmonic stenosis. ... Wieczorek et al. (1997) also described 2 other patients, provided a detailed review of previously reported cases, and discussed the differences from Noonan (see 163950) and Costello (218040) syndromes. Stark et al. (2012) reported 3 patients from 2 families with CFC2. ... The proband of the second family, who had an unaffected dizygotic twin, had a high birth weight, macrocephaly, and abnormal craniofacial features, including proptosis, hypertelorism, downslanting palpebral fissures, low-set ears, and short neck, suggestive of Noonan syndrome. Reexamination at age 3.5 years showed coarser facial features more consistent with CFC.
A number sign (#) is used with this entry because of evidence that cardiofaciocutaneous syndrome-4 (CFC4) is caused by heterozygous mutation in the MAPK2K2 gene (601263) on chromosome 19p13. For a general phenotypic description and a discussion of genetic heterogeneity of cardiofaciocutaneous syndrome, see CFC1 (115150). Description Cardiofaciocutaneous (CFC) syndrome is a multiple congenital anomaly disorder in which individuals have characteristic craniofacial features, cardiac defects, ectodermal anomalies, gastrointestinal dysfunction, and neurocognitive delay (summary by Rauen et al., 2010). ... Molecular Genetics Cardiofaciocutaneous syndrome most commonly occurs as a sporadic disorder, resulting from de novo heterozygous mutations in any of the 4 genes associated with the disorder.
A rare, multiple congenital anomalies syndrome characterized by craniofacial dysmorphology, congenital heart disease, dermatological abnormalities (most commonly hyperkeratotic skin and sparse, curly hair), neurological manifestations (hypotonia, seizures), failure to thrive and intellectual disability. ... Clinical description Cardiofaciocutaneous (CFC) syndrome displays wide phenotypic variability. ... In 50% of cases, seizures can also be present. Etiology CFC syndrome is considered a RASopathy and is due to mutations in one of the 4 genes: BRAF (7q34) (in 75% of CFC cases), MAP2K1 (15q22.1-q22.33), MAP2K2 (19p13.3), and KRAS (12p12.1), which encode proteins of the sarcoma/mitrogen-activated protein kinase (RAS/MAPK) signaling pathway. ... Differential diagnosis Differential diagnoses include Costello Syndrome (CS) and Noonan Syndrome, which have overlapping phenotypes with CFC syndrome. CFC syndrome, unlike CS, does not appear to have an increased risk of malignancies.
Genetic Heterogeneity of Parietal Foramina See also PFM2 (609597) and the 11p11.2 deletion syndrome (601224), in which parietal foramina are caused by haploinsufficiency of the ALX4 gene (605420) on chromosome 11p. ... Clinical Features Goldsmith (1922) called this condition 'Catlin marks' because he observed 16 instances in 5 generations of the Catlin family. This, like Hartnup disease, Cowdensyndrome, Lutheran trait, and Hageman factor, is one of the few examples of hereditary traits named for the family in which it was first observed. ... Chrzanowska et al. (1998) reported a patient with a 'new' branchial syndrome that included the features of parietal foramina; Rauch et al. (1998) considered the patient to represent a case of the FG syndrome (305450).
Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. 6. Excluding syndromic cases, sequence-level changes comprise the majority of pathogenic variants [Wilkie et al 2000; Wuyts et al 2000a; Wuyts et al 2000b; Mavrogiannis et al 2001; Spruijt et al 2005; Ghassibé et al 2006; Mavrogiannis et al 2006; Altunoglu et al 2014; Farwell et al 2015; Meng et al 2017; Lee et al 2018; T Lester & H Lord, unpublished data]. 7. ... Additionally, isolated enlarged parietal foramina need to be distinguished from unequivocal syndromic associations including those described in Table 4. Table 4. Autosomal Dominant Syndromes with Enlarged Parietal Foramina to Consider in the Differential Diagnosis of Isolated Enlarged Parietal Foramina View in own window Disorder Gene(s) / Genetic Mechanism Clinical Features Potocki-Shaffer syndrome (OMIM 601224) Proximal 11p deletion See Genetically Related Disorders ALX4 -related frontonasal dysplasia (OMIM 613451) ALX4 See Genetically Related Disorders MSX2 -related cleidocranial dysplasia (OMIM 168550) MSX2 See Genetically Related Disorders Saethre-Chotzen syndrome TWIST1 Craniosynostosis syndrome characterized by coronal synostosis, facial asymmetry, ptosis, & distinctive appearance of the ear Syndactyly of digits 2 & 3 of the hand variably present Enlarged parietal foramina are a less common manifestation. Acromelic frontonasal dysostosis (OMIM 603671) ZSWIM6 Severe frontonasal dysplasia & cranium bifidum / enlarged parietal foramina Preaxial polydactyly Cryptorchidism in males CDAGS syndrome (craniofacial dysplasia with genitourinary and skin abnormalities; OMIM 603116) may also be considered. Consensus features of this rare autosomal recessive syndrome are coronal synostosis, wide fontanelles and enlarged parietal foramina, hypoplasia of the clavicles, imperforate anus, and skin eruptions.
Parietal foramina also occur as part of the Potocki-Shaffer syndrome (601224), a contiguous gene syndrome caused by a deletion on chromosome 11p11.2 that includes the ALX4 gene. ... Mapping Using FISH, Wu et al. (2000) found a heterozygous deletion of a region corresponding to a BAC clone containing ALX4 on chromosome 11p in 2 patients with the Potocki-Shaffer syndrome. The authors stated that the involvement of Alx4 in murine skull development (Qu et al., 1997), its bone-specific expression pattern, the finding that Alx4 is a dosage-sensitive gene in the mouse, and the localization of a human genomic clone containing ALX4 to 11p11.2, with hemizygosity in patients with deletion of 11p11.2 who have biparietal foramina, supported the contention that ALX4 is a candidate gene for PFM in the Potocki-Shaffer syndrome.
Description Parietal foramina-3 is a nonsyndromic developmental defect characterized by symmetrical oval holes in the parietal bone (Chen et al., 2003). For a discussion of genetic heterogeneity of parietal foramina, see 168500. Clinical Features Chen et al. (2003) reported a large Chinese pedigree in which 15 individuals spanning 4 generations had typical features of nonsyndromic PFM. Inheritance The transmission pattern of parietal foramina in the family described by Chen et al. (2003) was consistent with autosomal dominant inheritance. Mapping By genomewide scanning in a Chinese family segregating PFM, Chen et al. (2003) identified a putative locus, termed PFM3, on chromosome 4q21-q23 (maximum 2-point lod score of 3.87 at marker D4S2961; maximum multipoint lod score of 6.17 between D4S2986 and D4S421).
EPF can also be accompanied by meningeal, cortical, and vascular malformations of the posterior fossa (that may predispose to epilepsy), and Duane retraction syndrome (see this term). Craniofacial anomalies including cleft palate, myelomeningocele and isolated encephalocele are rarely associated (see these terms). ... Differential diagnosis Differential diagnosis includes Potocki-Shaffer syndrome; distal monosomy 15q; cleidocranial dysplasia; acromelic frontonasal dysplasia; craniosynostosis-anal anomalies-porokeratosis; and frontonasal dysplasia with alopecia and genital anomaly (see these terms).
For a discussion of phenotypic and genetic heterogeneity of Griscelli syndrome, see Griscelli syndrome type 1 (GS1; 214450). ... In a review, Klein et al. (1994) stated that Griscelli syndrome can be distinguished from Chediak-Higashi syndrome by pathognomonic histologic features. ... In 8 Saudi Arabian kindreds, Harfi et al. (1992) described a disorder characterized by partial albinism with immunodeficiency and progressive demyelination of brain white matter, referred to as PAID syndrome. Although the authors originally considered this syndrome to be distinct from both Chediak-Higashi syndrome and Griscelli syndrome, de Saint Basile (2007) stated that 1 of the Saudi Arabian kindreds reported by Harfi et al. (1992) was found to have a mutation in the RAB27A gene. ... Aksu et al. (2003) noted that the presence of white matter disease and the absence of hemophagocytosis in their patient were unusual for a patient with mutation in the RAB27A gene, and extended the phenotypic spectrum of Griscelli syndrome. Diagnosis Durandy et al. (1993) successfully undertook the prenatal diagnosis of 2 hereditary syndromes associating albinism and immune defects: Chediak-Higashi syndrome and Griscelli syndrome. ... Menasche et al. (2002), Huizing et al. (2002), and Bahadoran et al. (2003, 2003) also suggested the identity of Elejalde syndrome, at least in some patients, and Griscelli syndrome type 1.
A rare subtype of Griscelli syndrome characterized by pigmentary dilution in skin and hair with irregular clumps of pigment in hair shafts resulting in silvery hair, in association with increased susceptibility to recurrent infections and immunological abnormalities, in particular impairment of T-cell and natural killer cytotoxic activity eventually leading to hemophagocytic lymphohistiocytosis. Patients may present neurological manifestations related to infiltration of the central nervous system in the context of the hemophagocytic syndrome. The disease is mostly fatal in the first decade of life.
Hereditary breast–ovarian cancer syndrome Other names HBOC Ovarian and breast cancer patients in a pedigree chart of a family Specialty Obstetrics and gynaecology , endocrinology , dermatology , oncology , medical genetics Hereditary breast–ovarian cancer syndromes ( HBOC ) are cancer syndromes that produce higher than normal levels of breast cancer , ovarian cancer and additional cancers in genetically related families (either one individual had both, or several individuals in the pedigree had one or the other disease). ... Mutations in BRCA1 are associated with a 39-46% risk of ovarian cancer and mutations in BRCA2 are associated with a 10-27% risk of ovarian cancer. [5] Other identified genes include: MLH1 , MSH2 , MSH6 , PMS2 : mutations in genes that lead to Lynch Syndrome put individuals at risk for ovarian cancer. [6] TP53 : Mutations cause Li-Fraumeni syndrome . It produces particularly high rates of breast cancer among younger women with mutated genes, and despite being rare, 4% of women with breast cancer under age 30 have a mutation in this gene. [4] PTEN : Mutations cause Cowdensyndrome , which produces hamartomas (benign polyps) in the colon, skin growths, and other clinical signs , as well as an increased risk for many cancers. [4] CDH1 : Mutations are associated with lobular breast cancer and gastric cancer . [4] STK11 : Mutations produce Peutz–Jeghers syndrome . ... ISBN 978-1-4987-4428-7 . ^ "Hereditary Breast Ovarian Cancer Syndrome (BRCA1 / BRCA2)" . Stanford University . ... (July 2019). "New name for breast-cancer syndrome could help to save lives" . Nature . 571 (7763): 27–29.
BRCA2 hereditary breast and ovarian cancer syndrome ( BRCA2 HBOC) is an inherited condition that is characterized by an increased risk for a variety of different cancers.
A number sign (#) is used with this entry because of evidence that susceptibility to familial breast-ovarian cancer-4 (BROVCA4) results from heterozygous germline mutation in the RAD51D gene (602954) on chromosome 17q11. For a discussion of genetic heterogeneity of breast-ovarian cancer susceptibility, see BROVCA1 (604370). For general discussions of breast cancer and ovarian cancer, see 114480 and 167000, respectively. Clinical Features Loveday et al. (2011) identified 8 families with breast-ovarian cancer associated with mutation in the RAD51D gene. Pathology information was available for 4 ovarian cancers from RAD51D mutation carriers; 3 of the cancers were serous adenocarcinoma and 1 was an endometrioid cancer.
A number sign (#) is used with this entry because susceptibility to familial breast-ovarian cancer-2 (BROVCA2) results from heterozygous germline mutations in the BRCA2 gene (600185) on chromosome 13q13. For a discussion of genetic heterogeneity of breast-ovarian cancer susceptibility, see BROVCA1 (604370). For general discussions of breast cancer and ovarian cancer, see 114480 and 167000, respectively. Clinical Features Wooster et al. (1994) reported a large family from Utah segregating early-onset breast cancer, ovarian cancer, and male breast cancer. Thorlacius et al. (1995) described a family with multiple cases of male breast cancer but no increase in female breast cancer.
Liede et al. (1998) raised the question of the existence of hereditary site-specific ovarian cancer as a genetic entity distinct from hereditary breast-ovarian cancer syndrome. They identified a large Ashkenazi Jewish kindred with 8 cases of ovarian carcinoma and no cases of breast cancer. ... Liede et al. (1998) concluded that site-specific ovarian cancer families probably represent a variant of the breast-ovarian cancer syndrome, attributable to mutation in either BRCA1 or BRCA2. ... Lynch and Watson (1992) reported extension of the linkage work to 19 families, most of which showed the hereditary breast-ovarian cancer syndrome. In 70% of families, linkage to 17q was demonstrated. ... Molecular Genetics In affected members of 5 of 8 kindreds with hereditary breast-ovarian cancer syndrome, Miki et al. (1994) identified 5 different heterozygous pathogenic mutations in the BRCA1 gene (see, e.g., 113705.0035). ... The single family with a BRCA2 mutation had the breast-ovarian cancer syndrome. Seven distinct mutations were identified; 5 of these occurred in 2 or more families.
Breast cancer (BC) is the most common cancer in women, accounting for 25% of all new cases of cancer. Most BC cases are sporadic, while 5-10% are estimated to be due to an inherited predisposition. Epidemiology Prevalence of germline BRCA mutations has been estimated to be about 1:1,600 women in the general population. The lifetime risk of developing hereditary BC (HBC) and/or OC can reach 80%. Clinical description HBC is not associated with specific phenotypic features.
BRCA1 hereditary breast and ovarian cancer syndrome ( BRCA1 HBOC) is an inherited condition that is characterized by an increased risk for a variety of different cancers.
A number sign (#) is used with this entry because susceptibility to familial breast-ovarian cancer-3 (BROVCA3) results from heterozygous germline mutation in the RAD51C gene (602774) on chromosome 17q21-q24. For a discussion of genetic heterogeneity of breast-ovarian cancer susceptibility, see BROVCA1 (604370). For general discussions of breast cancer and ovarian cancer, see 114480 and 167000, respectively. Clinical Features Meindl et al. (2010) identified 6 unrelated German pedigrees with breast-ovarian cancer associated with heterozygous germline mutations in the RAD51C gene. Each family had at least 2 affected women. The mean age of onset was 53 years (range 33 to 78) for breast cancer and 60 years (range 50 to 81) for ovarian cancer.
The differential diagnosis of other manifestations of IP includes the following disorders: Naegeli syndrome (OMIM 161000), a rare autosomal dominant disorder affecting the skin and skin derivatives, resembles IP, but also includes hyperhidrosis and punctate hyperkeratosis of the palms and soles. Unlike IP, Naegeli syndrome does not evolve through different stages of skin involvement. Naegeli syndrome is extremely rare; an individual with linear, wart-like lesions is more likely to have IP. Pathogenic variants in KRT14 cause Naegeli syndrome. Retinal neovascularization is observed in retinopathy of prematurity and familial exudative vitreoretinopathy, which can be inherited in an X-linked recessive manner as part of the Norrie disease spectrum (see OMIM 310600) or in an autosomal dominant manner (see Phenotypic Series: Exudative vitreoretinopathy).
By way of contrast, in the Aicardi syndrome (304050), X inactivation was apparently at random. ... IP in a male with XXY Klinefelter syndrome (Kunze et al., 1977) is consistent with this hypothesis. Ormerod et al. (1987) described incontinentia pigmenti in a boy with XXY Klinefelter syndrome. Pedigree patterns suggested X-linked dominance with lethality in the male.
An X-linked syndromic muti-systemic ectodermal dysplasia presenting neonatally in females with a bullous rash along Blaschko's lines (BL) followed by verrucous plaques and hyperpigmented swirling patterns. ... Differential diagnosis of stage II includes warts, molluscum contagiosum, and epidermal nevus syndrome. Any condition with 'linear and swirled' pigmentation overlaps with stage III. ... Additional reported differential diagnoses are Naegeli-Franceschetti-Jadassohn syndrome and Norrie's disease. Antenatal diagnosis Fertility is normal except for the miscarriage of affected males.
Incontinentia pigmenti is a condition that can affect many body systems, particularly the skin . This condition occurs much more often in females than in males. Incontinentia pigmenti is characterized by skin abnormalities that evolve throughout childhood and young adulthood. Many affected infants have a blistering rash at birth and in early infancy, which heals and is followed by the development of wart-like skin growths . In early childhood, the skin develops grey or brown patches (hyperpigmentation ) that occur in a swirled pattern. These patches fade with time, and adults with incontinentia pigmenti usually have lines of unusually light-colored skin (hypopigmentation) on their arms and legs.
Incontinentia pigmenti (IP) is a genetic condition that affects the skin and other body systems. Skin symptoms change with time and begin with a blistering rash in infancy, followed by wart-like skin growths. The growths become swirled grey or brown patches in childhood, and then swirled light patches in adulthood. Other signs and symptoms may include hair loss, small or missing teeth, eye abnormalities that can lead to vision loss, and lined or pitted nails. Most people with IP have normal intelligence, but some have developmental delay, intellectual disability, seizures, and/or other neurological problems.
Seckel syndrome is a genetic disorder characterized by growth retardation, very small head (microcephaly( with intellectual disability , and unique facial features such as large eyes, beak-like nose, narrow face, and receding lower jaw. About less than 25% of the patients also have blood abnormalities. Seckel syndrome is inherited in an autosomal recessive fashion.
A number sign (#) is used with this entry because of evidence that autosomal recessive primary microcephaly-13 (MCPH13) is caused by compound heterozygous mutation in the CENPE gene (117143) on chromosome 4q24. One such family has been reported. For a phenotypic description and a discussion of genetic heterogeneity of primary microcephaly, see MCPH1 (251200). Clinical Features Mirzaa et al. (2014) reported a brother and sister, born of unrelated parents of European descent, with microcephaly, poor overall growth, and developmental delay. Both had intrauterine growth retardation and microcephaly apparent on prenatal ultrasound, as well as similar dysmorphic facial features, including sloping forehead, prominent nose, and mild micrognathia. At age 5 years, the older sib, a boy, had microcephaly (-9 SD), short stature (-7 SD), small hands and feet, mild spasticity, and severely delayed psychomotor development with absent speech and poor gross and fine motor skills.
Seckel syndrome is a type of microcephalic primordial dwarfism that is characterized by a proportionate dwarfism of prenatal onset, a severe microcephaly, a typical dysmorphic face (bird-like), and mild to severe intellectual disability.
The report of a Seckel syndrome locus on chromosome 14q, designated SCKL3, by Kilinc et al. (2003) was found to be in error; see History section. ... Although some patients with Seckel syndrome manifest anemia and other hematologic abnormalities, AML had not previously been reported. Hayani et al. (1994) suggested that patients with Seckel syndrome may be at risk of developing myelodysplasia and AML. ... Heterogeneity Faivre et al. (2002) confirmed the heterogeneity of Seckel syndrome by excluding the previously mapped loci on chromosomes 3 and 18 in 5 consanguineous and 1 multiplex nonconsanguineous Seckel syndrome families. ... Associations Pending Confirmation For discussion of a possible association between Seckel syndrome and variation in the ATRIP gene, see 606605.0001.
A number sign (#) is used with this entry because of evidence that Seckel syndrome-9 (SCKL9) is caused by homozygous mutation in the TRAIP gene (605958) on chromosome 3p21. For a general phenotypic description and a discussion of genetic heterogeneity of Seckel syndrome, see SCKL1 (210600). Clinical Features Silengo et al. (2001) described 2 Italian sibs with a Seckel-like malformation syndrome characterized by intrauterine growth retardation (IUGR), microcephaly, beaked nose, failure to thrive, and early death. ... Additional whole-exome sequencing in 28 patients with a presumptive diagnosis of Seckel syndrome identified a Turkish boy who was homozygous for a missense mutation (R18C; 605958.0002) in the TRAIP gene.
Shaheen et al. (2014) noted the phenotypic similarities to Seckel syndrome (SCKL1; 210600). Inheritance The transmission pattern of MCCRP2 in the families reported by Martin et al. (2014) was consistent with autosomal recessive inheritance.
A number sign (#) is used with this entry because of evidence that Seckel syndrome-2 (SCKL2) is caused by homozygous mutation in the RBBP8 gene (604124) on chromosome 18q11. Jawad syndrome (251255), a microcephaly syndrome involving mental retardation and digital anomalies, is also caused by mutation in the RBBP8 gene. ... For a general phenotypic description and a discussion of genetic heterogeneity of Seckel syndrome, see SCKL1 (210600). Clinical Features Borglum et al. (2001) studied a consanguineous family of Iraqi descent with Seckel syndrome. The parents were first cousins and had 4 children who fulfilled the criteria for Seckel syndrome, as well as a younger healthy girl. ... In a 9-year-old Saudi Arabian girl with Seckel syndrome, Shaheen et al. (2014) identified homozygosity for a missense mutation in the RBBP8 gene (R100W; 604124.0004).
Woods et al. (1995) reported the case of an infant with pre- and postnatal microcephaly and growth retardation, a distinctive face, and developmental delay. Seckel syndrome was the initial diagnosis. The infant became pancytopenic at 16 months of age and died soon thereafter. ... Woods et al. (1995) proposed that this infant suffered from a distinct chromosome breakage syndrome. They found at least 7 reported cases of Seckel-like intrauterine growth retardation with pancytopenia, including 2 sibs in Seckel's original publication (Seckel, 1960). Other cases were reported by Upjohn (1955) and Butler et al. (1987). Because Seckel syndrome is likely to be heterogeneous, Woods et al. (1995) preferred to refer to the disorder they reported as 'severe intrauterine growth retardation with increased mitomycin C sensitivity.'
A number sign (#) is used with this entry because of evidence that Seckel syndrome-8 (SCKL8) is caused by homozygous mutation in the DNA2 gene (601810) on chromosome 10q21. One such family has been reported. Description Seckel syndrome is a rare autosomal recessive disorder characterized by intrauterine growth retardation, dwarfism, microcephaly with mental retardation, and a characteristic 'bird-headed' facial appearance (summary by Shanske et al., 1997). For a discussion of genetic heterogeneity of Seckel syndrome, see SCKL1 (210600). Clinical Features Shaheen et al. (2014) studied an uncle and niece, both born of consanguineous marriages, with short stature and strikingly similar facial features consistent with Seckel syndrome. ... Molecular Genetics In an uncle and niece with short stature and strikingly similar facial features consistent with Seckel syndrome, Shaheen et al. (2014) performed autozygome analysis and found a single shared run of homozygosity on chr10:63,850,661-71,470,390 (GRCh37).
A number sign (#) is used with this entry because Seckel syndrome-5 is caused by homozygous or compound heterozygous mutation in the CEP152 gene (613529) on chromosome 15q21. ... For a general phenotypic description and a discussion of genetic heterogeneity of Seckel syndrome, see 210600. Clinical Features Kalay et al. (2011) clinically evaluated 5 consanguineous families with Seckel syndrome originating from an isolated rural area in Turkey. ... Cranial magnetic resonance imaging in 2 patients showed simplified gyri. Inheritance Seckel syndrome-5 is an autosomal recessive disorder (Kalay et al., 2011). Mapping Using SNP array homozygosity mapping in 4 affected members of 3 Turkish families segregating Seckel syndrome, Kalay et al. (2011) obtained a lod score of 6.03 on chromosome 15q21.1-q21.2. ... By sequence analysis, Kalay et al. (2011) also identified compound heterozygous mutations in the CEP152 gene in affected Seckel syndrome patients of different ethnic origins (613529.0004-613529.0007).
A number sign (#) is used with this entry because of evidence that Seckel syndrome-4 (SCKL4) is caused by homozygous mutation in the CENPJ gene (609279) on chromosome 13q12. ... For a general description and a discussion of genetic heterogeneity of Seckel syndrome, see 210600. Clinical Features Al-Dosari et al. (2010) described a consanguineous Saudi family in which several members had clinical features of Seckel syndrome. ... Inheritance Consanguinity and affected sibs in the family with Seckel syndrome reported by Al-Dosari et al. (2010) were consistent with autosomal recessive inheritance. Mapping By homozygosity mapping and linkage analysis in a Saudi family with Seckel syndrome, Al-Dosari et al. (2010) mapped the locus for the disorder to chromosome 13q12 (maximum lod of 3.4). Molecular Genetics In affected members of a Saudi family segregating Seckel syndrome, Al-Dosari et al. (2010) identified a homozygous splicing mutation in the last nucleotide of intron 11 of the CENPJ gene (IVS11-1G-C; 609279.0004).
A third was associated with malformations suggestive of Meckel syndrome (249000): heart defect, pulmonary hypoplasia, renal dysplasia, and posterior encephalocele. ... Encha-Razavi et al. (1992) suggested the designation congenital hypothalamic hamartoma syndrome (CHHS) for a possibly familial disorder that combines orofacial abnormalities and skeletal dysplasia with hypothalamic hamartomas. ... Because approximately 5% of cases of hypothalamic hamartomas are associated with Pallister-Hall syndrome (PHS; 146510), which is caused by haploinsufficiency of GLI3, Craig et al. (2008) investigated the possibility that HH pathogenesis in sporadic cases is due to a somatic mutation in GLI3.
The conditions that they considered as related included Smith-Lemli-Opitz syndrome (270400), the pseudotrisomy 13 syndrome or holoprosencephaly-polydactyly syndrome (264480), orofaciodigital syndrome type VI or Varadi-Papp syndrome (277170), and the hydrolethalus syndrome (236680). ... Donnai et al. (1987) had suggested that the Pallister-Hall syndrome and severe Smith-Lemli-Opitz syndrome (270400) are the same disorder. Using multivariate analysis and numerical taxonomy, Verloes et al. (1995) concluded that on review, 'most overlapping cases (and, in fact, most cases reported as Pallister-Hall, including some from the original report)' could be unambiguously classified as Smith-Lemli-Opitz syndrome, orofaciodigital syndrome type VI (277170), or holoprosencephaly-polydactyly syndrome (264480). ... The radiologic abnormalities in the hand are helpful in differentiating Pallister-Hall syndrome from other syndromes in which hypothalamic hamartoblastoma is observed. ... Lurie (1995) questioned whether the Kaufmann-McKusick syndrome and the Pallister-Hall syndrome can be considered one entity.
Other symptoms of this tumor type include visual disturbances, such as the appearance of motion from a stationary object, or inappropriate color perception of the entire visual field. [6] Associated conditions [ edit ] Tuber cinereum hamartoma may be associated with Pallister-Hall syndrome , a diagnosis characterized by multiple malformations, including polydactyly and imperforate anus . ... External links [ edit ] Images of Hypothalamic Hamartoma v t e Phakomatosis Angiomatosis Sturge–Weber syndrome Von Hippel–Lindau disease Hamartoma Tuberous sclerosis Hypothalamic hamartoma ( Pallister–Hall syndrome ) Multiple hamartoma syndrome Proteus syndromeCowdensyndrome Bannayan–Riley–Ruvalcaba syndrome Lhermitte–Duclos disease Neurofibromatosis Type I Type II Other Abdallat–Davis–Farrage syndrome Ataxia telangiectasia Incontinentia pigmenti Peutz–Jeghers syndrome Encephalocraniocutaneous lipomatosis v t e Physiology of the endocrine system Regulatory systems Hypothalamic–pituitary–thyroid axis Hypothalamic–pituitary–adrenal axis Hypothalamic–pituitary–gonadal axis Hypothalamic–pituitary–somatotropic axis Hypothalamic–pituitary–prolactin axis Hypothalamic–neurohypophyseal system Renin–angiotensin system Metabolism Blood sugar regulation Calcium metabolism Fields Neuroendocrinology Pediatric endocrinology Psychoneuroendocrinology Reproductive endocrinology and infertility Other Wolff–Chaikoff effect / Jod-Basedow effect v t e Tumours of endocrine glands Pancreas Pancreatic cancer Pancreatic neuroendocrine tumor α : Glucagonoma β : Insulinoma δ : Somatostatinoma G : Gastrinoma VIPoma Pituitary Pituitary adenoma : Prolactinoma ACTH-secreting pituitary adenoma GH-secreting pituitary adenoma Craniopharyngioma Pituicytoma Thyroid Thyroid cancer (malignant): epithelial-cell carcinoma Papillary Follicular / Hurthle cell Parafollicular cell Medullary Anaplastic Lymphoma Squamous-cell carcinoma Benign Thyroid adenoma Struma ovarii Adrenal tumor Cortex Adrenocortical adenoma Adrenocortical carcinoma Medulla Pheochromocytoma Neuroblastoma Paraganglioma Parathyroid Parathyroid neoplasm Adenoma Carcinoma Pineal gland Pinealoma Pinealoblastoma Pineocytoma MEN 1 2A 2B
Though hypothalamic hamartomas can occur in patients with certain genetic disorders (such as Pallister-Hall syndrome ), the majority of cases are sporadic.