Ataxia-pancytopenia syndrome Specialty Neurology Ataxia-pancytopenia syndrome is a rare autosomal dominant disorder characterized by cerebellar ataxia , peripheral neuropathies , pancytopenia and a predilection to myelodysplastic syndrome and acute myeloid leukemia . Contents 1 Genetics 2 Diagnosis 3 History 4 References Genetics [ edit ] This syndrome is caused by mutations in the sterile alpha motif domain containing 9-like ( SAMD9L ) gene. [1] This gene is located on the long arm of chromosome 7 . Diagnosis [ edit ] This section is empty. You can help by adding to it . ( July 2018 ) History [ edit ] This syndrome was first described in 1981. [2] References [ edit ] ^ Chen DH, Below JE, Shimamura A, Keel SB, Matsushita M, Wolff J, Sul Y, Bonkowski E, Castella M, Taniguchi T, Nickerson D, Papayannopoulou T, Bird TD, Raskind WH (2016) Ataxia-Pancytopenia Syndrome Is Caused by Missense Mutations in SAMD9L. Am J Hum Genet 98(6):1146-1158. doi: 10.1016/j.ajhg.2016.04.009 ^ Li FP, Hecht F, Kaiser-McCaw B, Baranko PV, Potter NU (1981) Ataxia-pancytopenia: syndrome of cerebellar ataxia, hypoplastic anemia, monosomy 7, and acute myelogenous leukemia. Cancer Genet Cytogenet 4(3):189-196

Ataxia-pancytopenia syndrome is a rare condition that affects the part of the brain that coordinates movement (the cerebellum) and blood-forming cells in the bone marrow . The age when signs and symptoms begin, the severity of the condition, and the rate at which it worsens all vary among affected individuals. People with ataxia-pancytopenia syndrome have neurological problems associated with a loss of tissue (atrophy) and other changes in the cerebellum. These problems include poor coordination and balance (ataxia), difficulty with movements that involve judging distance or scale (dysmetria), uncontrollable muscle contractions (clonus), and involuntary back-and-forth eye movements (nystagmus). These neurological issues worsen over time, making walking and other movements challenging.

A rare genetic disease characterized by cerebellar ataxia, cytopenias and predisposition to bone marrow failure and myeloid leukaemia. Neurologic features variably include slowly progressive cerebellar ataxia or balance impairment with cerebellar atrophy and periventricular white matter T2 hyperintensities in brain MRI, horizontal and vertical nystagmus, dysmetria, dysarthria, pyramidal tract signs and reduced nerve conduction velocity. Hematological abnormalities are variable and may be intermittent and include cytopenias of all cell lineages, immunodeficiency, myelodysplasia and acute myeloid leukemia.

A rare, respiratory malformation characterized by defective or completely absent bronchial wall cartilage in subsegmental bronchi, leading to distal airway collapse and contributing to the formation of bronchiectasis. The defect is mostly present between the fourth and sixth order bronchial divisions. Clinical manifestation includes recurrent pneumonia, coughing and wheezing.

Williams–Campbell syndrome Other names Bronchomalacia Usual onset Typically childhood Causes Genetic mutation Risk factors Family history Diagnostic method Diagnosis of exclusion , Bronchoscopy Prevention None Treatment Lung transplantation Frequency Unknown but extremely rare Williams–Campbell syndrome (WCS) is a disease of the airways where cartilage in the bronchi is defective. It is a form of congenital cystic bronchiectasis . This leads to collapse of the airways and bronchiectasis . [1] It acts as one of the differential to Allergic bronchopulmonary aspergillosis . WCS is a deficiency of the bronchial cartilage distally. [2] Contents 1 Symptoms 2 Pathology 3 Diagnosis 4 Treatment 4.1 Lung transplantation 4.2 Lobectomy 4.3 Medicine 5 History 6 References 7 External links Symptoms [ edit ] Persistent cough Wheeze Impaired lung function [2] Pathology [ edit ] It is thought to result from a deficiency of cartilage formation in the 4th to 6th order segmental bronchi. [3] Diagnosis [ edit ] Most described cases present sporadically in early childhood. [3] However, some have been diagnosed as late as adulthood. [4] [5] [6] Due to its rarity it presents a difficulty in adult diagnoses, and its initial presentation can be confused with septic shock . [7] Diagnosis requires an appropriate clinical history , the characteristic expiratory airway collapse on radiological investigation, and exclusion of other causes of congenital and acquired bronchiectasis . Pathology of the affected bronchi by bronchoscopy showing the deficiency of cartilaginous plates in the bronchial wall is the confirmatory test . [3] However, lung biopsy has several complications and is not always diagnostic. [ citation needed ] Considering its non-invasive methodology, facility of execution, and good patient tolerance, multi-slice spiral CT or CT bronchoscopy should be the test of choice to study cystic lung diseases in particular WCS. [3] Radiologically, the lungs are overinflated , and on bronchoscopy bronchomalacia is demonstrated. [2] Treatment [ edit ] In 2011, Hacken et al. conducted a systematic review, aiming to answer what are the effects of treatments in people with bronchiectasis but without cystic fibrosis. There are not enough studies to prove if bronchopulmonary hygiene, physical therapy , mucolytics , inhaled hyperosmolar agents, oral corticosteroids , leukotriene receptor antagonists , short-acting beta 2 agonists , long-acting beta 2 agonists, or anticholinergic therapy is beneficial. [8] However, there are some promising results in other approaches.

Tracheobronchomalacia (TBM) is a rare condition that occurs when the walls of the airway (specifically the trachea and bronchi ) are weak. This can cause the airway to become narrow or collapse. There are two forms of TBM. One typically develops during infancy or early childhood (primary TBM). The other is an acquired form usually seen in adults (acquired or secondary TBM). Some people with TBM may initially have no signs or symptoms. However, the condition typically is progressive (worsening over time) and most people will eventually develop shortness of breath, cough, sputum retention (inability to clear mucus from the respiratory tract), and/or wheezing or stridor with breathing.

In 4 of 5 brothers, Agosti et al. (1974) observed chronic respiratory distress in early infancy and showed in one that it was due to bronchial flaccidity. Because of the bronchomalacia, first and second generation bronchi almost collapsed during expiration. Air trapping and respiratory distress simulated bronchial asthma. The parents were not known to be related but had the same surname and originated from the same small village in Italy. Wayne and Taussig (1976) described 2 sibs with respiratory symptoms dating from birth and subsequently demonstrated bronchiectasis. They postulated absence of bronchial cartilage.

Hemimegalencephaly is a rare cerebral malformation characterized by overgrowth of all or part of a cerebral hemisphere, often with ipsilateral severe cortical dysplasia or dysgenesis, white matter hypertrophy and dilated lateral ventricle, presenting in early infancy with progressive hemiparesis, severe psychomotor retardation and intractable seizures. Hemimegalencephaly may be an isolated finding or associated with other syndromes such as angioosteohypertrophic syndrome, epidermal nevus syndrome and Ito hypomelanosis (see these terms). Management includes seizure control by antiepileptic medications and early hemispherectomy.

Hemimegalencephaly is a rare malformation involving one side of the brain. It may occur alone or in association with other syndromes such as Proteus syndrome , tuberous sclerosis , linear sebaceous nevus syndrome , neurofibromatosis , Sturge-Weber syndrome , or Klippel-Trenaunay syndrome . Children with this disorder may have a large, asymmetrical head accompanied by seizures, partial paralysis, and impaired cognitive development. Because the seizures associated with hemimegalencephaly are difficult to treat with anticonvulsant medications, a surgery called hemispherectomy is often the most successful treatment. The cause of hemimegalencephaly is not fully understood, but involves a disturbance of cells early in development and likely involves genes involved in patterning and symmetry.

Frontal fibrosing alopecia (FFA) is a form of lichen planopilaris that is characterized primarily by slowly progressive hair loss ( alopecia ) and scarring on the scalp near the forehead. In some cases, the eyebrows, eye lashes and/or other parts of the body may be involved, as well. Although it has been suggested that FFA may be due to hormonal changes or an autoimmune response , the exact cause of this condition is not yet known. There is currently no cure for FFA; however, treatment with certain types of medications may stop or slow hair loss in some cases.

Frontal fibrosing alopecia (FFA) is a rare variant of lichen planopilaris (see this term) characterized by symmetrical, progressive, band-like anterior hair loss of the scalp. Epidemiology Prevalence is unknown. It most commonly affects postmenopausal women, although it has also been reported in men and premenopausal women. Clinical description Progressive recession of the frontal and temporal hairline is observed. Approximately half of all cases of FFA also have eyebrow loss; less often there is hair loss in other parts of the body. It is only very rarely associated with classic lichen planus lesions elsewhere.

Erysipeloid of Rosenbach Specialty Dermatology Erysipeloid of Rosenbach is a cutaneous condition most frequently characterized by a purplish marginated swelling on the hands. [1] : 264 History [ edit ] The eponym Rosenbach's disease is in reference to the milder type of the condition and is named after Friedrich Julius Rosenbach . [2] Klauder's syndrome I is a syndrome of severe systemic involvement, and is named after Joseph Victor Klauder . [3] See also [ edit ] Erysipeloid Skin lesion References [ edit ] ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology . Saunders Elsevier. ISBN 0-7216-2921-0 . ^ Rosenbach's disease at Who Named It? ^ Klauder's syndrome I at Who Named It? This infection-related cutaneous condition article is a stub . You can help Wikipedia by expanding it . v t e

Partial response to erlotinib in a patient with imatinib-refractory sacral chordoma. Clin Sarcoma Res 10, 28 (2020). https://doi.org/10.1186/s13569-020-00149-1 ^ Gröschel S, Hübschmann D, Raimondi F, Horak P, Warsow G, Fröhlich M, Klink B, Gieldon L, Hutter B, Kleinheinz K, Bonekamp D, Marschal O, Chudasama P10,11, Mika J, Groth M, Uhrig S, Krämer S, Heining C, Heilig CE, Richter D, Reisinger E, Pfütze K, Eils R, Wolf S, von Kalle C, Brandts C, Scholl C, Weichert W, Richter S, Bauer S, Penzel R, Schröck E, Stenzinger A, Schlenk RF, Brors B, Russell RB, Glimm H, Schlesner M, Fröhling S (2019) Defective homologous recombination DNA repair as therapeutic target in advanced chordoma.

Chordomas are rare malignant tumors arising from embryonic remnants of the notochord in axial skeleton. Epidemiology They are predominantly found in adults, and comprise 0.2% of all central nervous system tumors and 2-4% of all primary bone neoplasms, with an estimated prevalence of 1 in 2 million people and a male-to-female ratio of 2:1. Clinical description The clinical presentation depends entirely on the location of the chordoma. The main possible locations are the sacrum, intracranially at the clivus and along the spinal axis. When the tumor is intracranial, the most common presenting symptoms are diplopia, swallowing problems and headache.

A chordoma is a rare tumor that develops from cells of the notochord, a structure that is present in the developing embryo and is important for the development of the spine. The notochord usually disappears before birth, though a few cells may remain embedded in the bones of the spine or at the base of the skull. Chordomas typically present in adults between the ages of 40 and 70 and can occur anywhere along the spine. About half of all chordomas occur at the bottom of the spine (sacrum); about one third occur at the base of the skull. The remaining cases of chordomas form in the spine at the level of the neck, chest, or other parts of the lower back.

A number sign (#) is used with this entry because autosomal recessive dyskeratosis congenita-2 (DKCB2) is caused by homozygous or compound heterozygous mutation in the NOLA2 gene (606470), also known as NHP2, on chromosome 5q35. Description Dyskeratosis congenita is a multisystem disorder caused by defective telomere maintenance. Clinical manifestations include mucocutaneous abnormalities, bone marrow failure, and an increased predisposition to cancer, among other variable features (summary by Vulliamy et al., 2008). For a discussion of genetic heterogeneity of dyskeratosis congenita, see DKCA1 (127550). Clinical Features Vulliamy et al. (2008) reported a Turkish man with nail dystrophy, thrombocytopenia, testicular atrophy, opportunistic infections, growth and mental retardation, liver cirrhosis, and intracranial calcification.

A number sign (#) is used with this entry because autosomal recessive dyskeratosis congenita-3 (DKCB3) is caused by compound heterozygous mutation in the TCAB1 gene (WRAP53; 612661) on chromosome 17p13. Description Dyskeratosis congenita is a genetic disorder of defective tissue maintenance, impaired stem cell function, and cancer predisposition caused by short telomeres resulting from a defect in telomerase. Clinical manifestations may be seen in the skin as leukoplakia, nail dystrophy, and reticular pigmentation, in the bone marrow as pancytopenia, and in the lung as pulmonary fibrosis, as well as in other tissues (summary by Zhong et al., 2011). For a discussion of genetic heterogeneity of dyskeratosis congenita, see DKCA1 (127550). Clinical Features Zhong et al. (2011) reported 2 unrelated patients with the classic triad of DKC, including oral leukoplakia, abnormal skin pigmentation, and nail dystrophy.

Dyskeratosis congenita affects many parts of the body. Three features are especially characteristic of this disorder: (1) fingernails and toenails that grow poorly or are abnormally shaped; (2) changes in skin coloring (pigmentation), especially on the neck and chest, that resembles the appearance of lace; and (3) white patches inside the mouth (oral leukoplakia). People with dyskeratosis congenita also have an increased risk of developing several life-threatening conditions, including pulmonary fibrosis, bone marrow failure, aplastic anemia, myelodysplastic syndrome, leukemia, and other cancers. The severity of dyskeratosis congenita varies widely among affected individuals. This condition is caused by pathogenic variants (mutations) in a number of different genes known to affect the length of the telomeres. Telomeres are structures found at the ends of chromosomes that protect the chromosomes from sticking together or breaking down.

INHERITANCE - Autosomal dominant HEAD & NECK Mouth - Leukoplakia Teeth - Dental caries - Early tooth loss RESPIRATORY Lung - Pulmonary fibrosis - Interstitial pneumonitis ABDOMEN Liver - Liver cirrhosis SKIN, NAILS, & HAIR Skin - Reticulate hyperpigmentation - Skin atrophy Nails - Nail dystrophy - Nail ridging - Nail pitting Hair - Hair loss - Premature graying - Sparse hair - Alopecia HEMATOLOGY - Bone marrow failure - Aplastic anemia - Lymphopenia - Pancytopenia - Anemia - Thrombocytopenia - Elevated MCV - Hypoplastic myelodysplasia NEOPLASIA - Squamous cell carcinoma of the skin LABORATORY ABNORMALITIES - Shortened telomeres MISCELLANEOUS - Highly variable phenotype - Variable penetrance and expressivity - Genetic anticipation associated with progressive telomere shortening - Skin manifestations may not be present - Median age of diagnosis is 28 years - Median survival is > 50 years MOLECULAR BASIS - Caused by mutation in the telomerase RNA component gene (TERC, 602322.0001 ) ▲ Close

Dyskeratosis congenita Other names Zinsser-Cole-Engman syndrome , [1] [2] : 570 Dyskeratosis congenital is inherited in an X-linked recessive manner Specialty Medical genetics Dyskeratosis congenita ( DKC ),also known as Zinsser-Engman-Cole syndrome, is a rare progressive congenital disorder with a highly variable phenotype . [3] The entity was classically defined by the triad of abnormal skin pigmentation, nail dystrophy , and leukoplakia of the oral mucosa , but these components do not always occur. [3] DKC is characterized by short telomeres . Some of the manifestations resemble premature ageing (similar to progeria ). The disease initially mainly affects the skin , but a major consequence is progressive bone marrow failure which occurs in over 80%, causing early mortality. [3] Contents 1 Presentation 1.1 Predisposition to cancer 2 Genetics 2.1 X-linked 2.2 Autosomal dominant 2.3 Autosomal recessive 3 Pathophysiology 4 Diagnosis 5 Management 6 Prognosis 7 Research 8 See also 9 References 10 External links Presentation [ edit ] This section does not cite any sources . Please help improve this section by adding citations to reliable sources . Unsourced material may be challenged and removed . ( January 2018 ) ( Learn how and when to remove this template message ) DKC can be characterized by cutaneous pigmentation, premature graying, dystrophy of the nails , leukoplakia of the oral mucosa, continuous lacrimation due to atresia of the lacrimal ducts , often thrombocytopenia , anemia , testicular atrophy in the male carriers, and predisposition to cancer .

A rare ectodermal dysplasia syndrome that often presents with the classic triad of nail dysplasia, skin pigmentary changes, and oral leukoplakia associated with a high risk of bone marrow failure (BMF) and cancer. Epidemiology Dyskeratosis congenita (DC) prevalence is unknown. More than 400 families are reported in the world. Clinical description DC has a wide phenotypic spectrum and age onset. It classically manifests during childhood with the triad of dysplastic nails, lacy reticular pigmentation and atrophy of the skin at the level of the neck and upper chest, and oral leukoplakia. Patients are at high risk of progressive BMF and may develop myelodysplastic syndrome or acute myelogenous leukemia at any age (the risk increasing with age).

Most solid tumors develop after the first decade (median age of onset: 28 years). Monthly self-examination for oral, head, and neck cancer Annual cancer screening by an otolaryngologist Annual gynecologic examination Annual skin cancer screening by a dermatologist Pulmonary fibrosis.

A number sign (#) is used with this entry because of evidence that Galloway-Mowat syndrome-8 (GAMOS8) is caused by homozygous mutation in the NUP133 gene (607613) on chromosome 1q42. One such family has been reported. Biallelic mutation in the NUP133 gene can also cause nephrotic syndrome type 18 (NPHS18; 618177). Description Galloway-Mowat syndrome-8 is an autosomal recessive disorder characterized by impaired psychomotor development, poor overall growth with microcephaly, and early-onset progressive nephrotic syndrome associated with focal segmental glomerulosclerosis on renal biopsy. Some patients may have seizures, and some may die in childhood (summary by Fujita et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of GAMOS, see GAMOS1 (251300).

A number sign (#) is used with this entry because of evidence that Galloway-Mowat syndrome-4 (GAMOS4) is caused by homozygous or compound heterozygous mutation in the TP53RK gene (608679) on chromosome 20q13. Description Galloway-Mowat syndrome is a renal-neurologic disease characterized by early-onset nephrotic syndrome associated with microcephaly, gyral abnormalities, and delayed psychomotor development. Most patients have dysmorphic facial features, often including hypertelorism, ear abnormalities, and micrognathia. Other features, such as arachnodactyly and visual impairment, are more variable. Most patients die in the first years of life (summary by Braun et al., 2017).

One patient had hypoplastic left heart, aortic coarctation, coloboma, arachnodactyly, and ichthyosis, which may have resulted from a concurrent 1q21.1 duplication of several genes that occurred only in this patient and not in the sib. Braun et al. (2017) reported 28 patients from 24 families with GAMOS3.

A number sign (#) is used with this entry because of evidence that X-linked Galloway-Mowat syndrome-2 (GAMOS2) is caused by hemizygous mutation in the LAGE3 gene (300060) on chromosome Xq28. Description Galloway-Mowat syndrome is a renal-neurologic disease characterized by early-onset nephrotic syndrome associated with microcephaly, gyral abnormalities of the brain, and delayed psychomotor development. Most patients have dysmorphic facial features, often including hypertelorism, ear abnormalities, and micrognathia. Other features, such as arachnodactyly and visual impairment, are more variable. Most patients die in the first years of life (summary by Braun et al., 2017).

A number sign (#) is used with this entry because of evidence that Galloway-Mowat syndrome-5 (GAMOS5) is caused by homozygous mutation in the TPRKB gene (608680) on chromosome 2p13. Description Galloway-Mowat syndrome is a renal-neurologic disease characterized by early-onset nephrotic syndrome associated with microcephaly, gyral abnormalities, and delayed psychomotor development. Most patients have dysmorphic facial features, often including hypertelorism and ear abnormalities. Other features, such as arachnodactyly and visual or hearing impairment, are more variable. Most patients die in the first years of life (summary by Braun et al., 2017).

A rare, genetic multisystem disorder characterized by a neurodegenerative disorder associating global developmental delay, progressive microcephaly, and progressive cerebral and cerebellar atrophy with extrapyramidal involvement, progressive optic atrophy, and in many patients early-onset steroid-resistant nephrotic syndrome. Epidemiology More than 100 cases have been reported to date. Males and females are equally affected. Clinical description Disease onset is typically within the first few months of life, but may be detected in childhood with later onset nephrotic syndrome (NS). Clinical manifestations, primarily involving the kidney and central nervous system, are heterogeneous. Renal manifestations range from isolated proteinuria to full blown early-onset nephrotic syndrome (NS), which is multidrug resistant and rapidly progresses to end-stage kidney disease (ESKD).

Galloway-Mowat syndrome is a rare, neurodegenerative disorder characterized by various developmental and physical abnormalities. Signs and symptoms may include small head size (microcephaly); developmental delay; seizures; nephrotic syndrome ; hiatal hernia ; optic atrophy ; movement disorders ; and intellectual disability. Other physical abnormalities may also be present. Galloway-Mowat syndrome may be caused by changes (mutations) in the WDR73 gene and is inherited in an autosomal recessive manner. Other, unknown genes may also be responsible. Affected children often do not survive beyond the first few years of life. Treatment is aimed at the specific signs and symptoms present in each individual.

A number sign (#) is used with this entry because of evidence that Galloway-Mowat syndrome-6 (GAMOS6) is caused by homozygous or compound heterozygous mutation in the WDR4 gene (605924) on chromosome 21q22. Description Galloway-Mowat syndrome is a phenotypically heterogeneous disorder characterized by neurodevelopmental defects combined with renal-glomerular disease manifest as nephrotic syndrome and proteinuria. Most patients with GAMOS6 also have growth deficiency with variable microcephaly, and the renal disease may be age-dependent. Additional variable endocrine abnormalities have also been reported (summary by Braun et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of GAMOS, see GAMOS1 (251300).

Galloway Mowat syndrome Other names Galloway Syndrome, Hiatal Hernia-Microcephaly-Nephrosis, Galloway Type, Microcephaly-Hiatal Hernia-Nephrosis, Galloway Type, Nephrosis-Microcephaly Syndrome, Nephrosis-Neuronal Dysmigration Syndrome, Microcephaly-Hiatal Hernia-Nephrotic Syndrome Galloway Mowat syndrome has an autosomal recessive pattern of inheritance . Galloway Mowat syndrome is a very rare autosomal recessive [1] genetic disorder, consisting of a variety of features including hiatal hernia , microcephaly and nephrotic syndrome . [2] Contents 1 Cause 2 Genetics 3 Diagnosis 4 Treatment 5 References 6 External links Cause [ edit ] The exact genetic defect in Galloway Mowat syndrome is yet to be discovered. However, mutations in podocyte proteins, such as nephrin , alpha-actinin 4 , and podocin , are associated with proteinuria and nephrotic syndrome. There is reduced expression of synaptopodin , GLEPP1 , and nephrin in Galloway-Mowat syndrome, but these are likely secondary to the proteinuria, likely not the proteins mutated in Galloway-Mowat syndrome. [3] The biochemical lesion appears to be in the Kinase, Endopeptidase and Other Proteins of small Size (KEOPS)/Endopeptidase-like and Kinase associated to transcribed Chromatin (EKC) ( KEOPS/EKC ) complex. [4] Sequencing of genes in 37 cases of this condition revealed mutations in the OSGEP , TP53RK , TPRKB and LAGE3 genes all of which encode subunits in the KEOPS complex. Members of this complex are found in bacteria, archaea and eukaryotes and are highly conserved.

A number sign (#) is used with this entry because of evidence that Galloway-Mowat syndrome-7 (GAMOS7) is caused by homozygous or compound heterozygous mutation in the NUP107 gene (607617) on chromosome 12q15. Biallelic mutation in the NUP107 gene can also cause nephrotic syndrome type 11 (NPHS11; 616730). Description Galloway-Mowat syndrome-7 (GAMOS7) is an autosomal recessive disorder characterized by developmental delay, microcephaly, and early-onset nephrotic syndrome (summary by Rosti et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of GAMOS, see GAMOS1 (251300). Clinical Features Rosti et al. (2017) reported 5 patients from 2 unrelated consanguineous families, one of which was of Turkish descent, with a nephrotic syndrome similar to Galloway-Mowat syndrome.

An aggressive soft tissue cancer that typically arises in serous lined surfaces of the abdominal or pelvic peritoneum, and spreads to the omentum, lymph nodes and hematogenously disseminates especially to the liver. Extraserous primary location has been reported in exceptional cases. Epidemiology DSRCT is extremely rare. Only a few hundred cases have been reported worldwide since the first description in 1989. It usually affects males, during adolescence or young adulthood, with a male-to-female ratio of 4:1. Clinical description Clinical signs and symptoms of DSRCT are non-specific.

Desmoplastic small round cell tumor (DSRCT) is a rare type of soft tissue cancer (sarcoma) that usually begins in the abdomen. It primarily affects children and young adults and is more common in males. It is formed by small, round cancer cells surrounded by scar-like tissue and is often found in the tissue (peritoneum) that lines the inside of the abdomen and pelvis. The tumor cells have a characteristic genetic change involving a translocation between chromosomes 11 and 22 , which is important in differentiating from other similar tumors. The genetic change involved in DSRCT is acquired throughout a person's lifetime and is not inherited.

Overhydrated hereditary stomatocytosis (OHSt) is a disorder of red cell membrane permeability to monovalent cations and is characterized clinically by hemolytic anemia. Epidemiology OHSt is very rare with only seven cases described in the literature so far. Clinical description Onset occurs during the neonatal period or infancy with hemolytic anemia that may require occasional blood transfusions. Splenomegaly or hepatosplenomegaly are present. The disease course is marked by the usual complications of hemolytic anemia (biliary lithiasis) and, remarkably, by a strong tendency for iron overload. Etiology In the majority of cases, OHSt is caused by mutations in the RHAG gene (6p21-qter) encoding the Rh-associated glycoprotein component of the Rh complex.

X-linked infantile nystagmus is a condition characterized by abnormal eye movements. Nystagmus is a term that refers to involuntary side-to-side movements of the eyes. In people with this condition, nystagmus is present at birth or develops within the first six months of life. The abnormal eye movements may worsen when an affected person is feeling anxious or tries to stare directly at an object. The severity of nystagmus varies, even among affected individuals within the same family.

Restless legs syndrome is a neurological condition that causes an irresistible urge to move the legs. The movement is triggered by strange or uncomfortable feelings, often described as crawling, pulling, or itching, deep within both legs. The feelings usually occur while the affected person is sitting or lying down and are worse at night. Movement, such as kicking, stretching, rubbing, or pacing, make the discomfort go away, at least temporarily. The unpleasant feelings and the resulting need to move the legs often make it difficult for an affected person to fall asleep or stay asleep.

A number sign (#) is used with this entry because of evidence that susceptibility to epidermodysplasia verruciformis-3 (EV3) is conferred by homozygous mutation in the CIB1 gene (602293) on chromosome 15q26. Description Epidermodysplasia verruciformis-3 is characterized by onset in childhood or early adulthood of persistent disseminated flat warts and pityriasis versicolor-like lesions of the skin that are induced by cutaneous human papillomaviruses (HPVs) of the beta genus. Some patients develop nonmelanoma skin cancer, particularly on areas of the body exposed to the sun. Patients are otherwise healthy and normally resistant to other microorganisms, including other viruses and skintropic pathogens, and even all other cutaneous and mucosal HPVs (de Jong et al., 2018). For a discussion of genetic heterogeneity of susceptibility to epidermodysplasia verruciformis, see EV1 (226400).

Epidermodysplasia verruciformis (EV) is a rare inherited genodermatosis characterized by chronic infection with human papillomavirus (HPV) leading to polymorphous cutaneous lesions and high risk of developing non melanoma skin cancer. Epidemiology The exact prevalence of EV is unknown; more than 200 cases have been reported in the literature so far. Clinical description The disease usually manifests during infancy (7.5% of cases), childhood (61.5% of cases) or puberty (22% of cases) with a progressive development of hyperpigmented or hypopigmented flat wart-like papules, irregular reddish brown plaques, seborrheic keratosis-like lesions and pityriasis versicolor-like macules on the trunk, neck, face, dorsal hands and feet (sun-exposed skin). Various HPV subtypes (HPV5 and HPV8 are found in 80% of cases) can be detected in the cutaneous lesions. Thirty to 60% of patients develop non-melanoma skin cancers, especially squamous cell carcinomas (SCC), during the fourth or fifth decades of life, mainly on sun-exposed areas.

A number sign (#) is used with this entry because of evidence that susceptibility to epidermodysplasia verruciformis-2 (EV2) is conferred by homozygous mutation in the TMC8 gene (605829) gene on chromosome 17q25. Description Epidermodysplasia verruciformis (EV) is a rare genodermatosis associated with a high risk of skin cancer. EV results from an abnormal susceptibility to specific related human papillomavirus (HPV) genotypes and to the oncogenic potential of some of them, mainly HPV5. Infection with EV-associated HPV leads to the early development of disseminated flat wart-like and pityriasis versicolor-like lesions. Patients are unable to reject their lesions, and cutaneous Bowen carcinomas in situ and invasive squamous cell carcinomas develop in about half of them, mainly on sun-exposed areas (summary by Ramoz et al., 2000).

A number sign (#) is used with this entry because of evidence that susceptibility to epidermodysplasia verruciformis-1 (EV1) is conferred by homozygous or compound heterozygous mutation in the TMC6 gene (605828) on chromosome 17q25. Description Epidermodysplasia verruciformis (EV) is a rare genodermatosis associated with a high risk of skin cancer. EV results from an abnormal susceptibility to specific related human papillomavirus (HPV) genotypes and to the oncogenic potential of some of them, mainly HPV5. Infection with EV-associated HPV leads to the early development of disseminated flat wart-like and pityriasis versicolor-like lesions. Patients are unable to reject their lesions, and cutaneous Bowen carcinomas in situ and invasive squamous cell carcinomas develop in about half of them, mainly on sun-exposed areas (summary by Ramoz et al., 2000).

Androphy et al. (1985) described a kindred in which a 56-year-old man had EDV, none of his 5 sons or 5 daughters had EDV, and 4 of his grandsons (through 2 daughters) had EDV. All were infected with human papillomavirus 3 (HPV 3) and with HPV 8. The proband, who had onset of warts at age 5 years with no regression over the next 50 years and with extension to cover about 10% of his skin surface, had squamous carcinoma arising on sun-exposed areas of the face, ears, neck, back, arms, and hands over the previous 25 years. Other pedigrees have suggested autosomal inheritance although whether dominant as suggested by some families or recessive as suggested by parental consanguinity (see 226400) is not certain. Inheritance - X-linked form Skin - Epidermodysplasia verruciformis - Human papillomavirus (HPV 3 and HPV 8) infection - Warts - Squamous skin carcinoma ▲ Close

A number sign (#) is used with this entry because of evidence that susceptibility to epidermodysplasia verruciformis-5 (EV5) is conferred by homozygous mutation in the IL7 gene (146660) on chromosome 8q21. One such family has been reported. Description Epidermodysplasia verruciformis-5 is an autosomal recessive immunologic disorder characterized by onset of warts and verrucous or plaque-like skin lesions associated with HPV infection. Immunologic workup shows T-cell lymphopenia, particularly affecting CD4+ T cells. There is an increased risk of skin malignancy, and some patients may have other symptoms of immune dysfunction (summary by Horev et al., 2015). For a discussion of genetic heterogeneity of susceptibility to epidermodysplasia verruciformis, see EV1 (226400).