Lethal congenital contracture syndrome type 2 is a rare arthrogryposis syndrome characterized by multiple congenital contactures (typically extended elbows and flexed knees), micrognathia, anterior horn cell degeneration, skeletal muscle atrophy (mainly in the lower limbs), presence of a markedly distended urinary bladder and absence of hydrops, pterygia and bone fractures.
A number sign (#) is used with this entry because of evidence that lethal congenital contracture syndrome-2 (LCCS2) can be caused by homozygous mutation in the ERBB3 gene (190151) on chromosome 12q13. ... Because a similar form of autosomal recessive lethal congenital contractural syndrome (LCCS3; 611369) is caused by a mutation in the PIP5K1C gene (606102), which encodes phosphatidylinositol-4-phosphate 5-kinase, type I, gamma (PIKI-gamma), Narkis et al. (2007) sequenced 2 genes within the LCCS2 locus on the basis of their association with the phosphatidylinositol pathway.
Familial episodic pain syndrome with predominantly lower limb involvement is a subtype of familial episodic pain syndrome characterized by intense, episodic and/or cyclic pain mainly localized in the distal lower limbs (occasionally affecting upper limbs as well) which is triggered/exacerbated by fatigue, cold exposure and/or weather changes and alleviated with anti-inflammatory medication, that has a tendancy to diminish in frequency with age.
A number sign (#) is used with this entry because of evidence that familial episodic pain syndrome-3 (FEPS3) is caused by heterozygous mutation in the SCN11A gene (604385) on chromosome 3p22. Description Familial episodic pain syndrome is an autosomal dominant disorder characterized by early childhood onset of intense episodic pain mainly affecting the distal lower extremities, but sometimes affecting the upper extremities as well. ... For a discussion of the genetic heterogeneity of familial episodic pain syndrome, see FEPS1 (615040). Clinical Features Zhang et al. (2013) reported 2 unrelated large multigenerational Chinese families with a similar episodic pain syndrome with onset in early childhood. ... Three of the patients had significant comorbid medical problems, including Alport syndrome (203780), primary biliary cirrhosis, and colorectal cancer that was not treated with chemotherapy. ... Molecular Genetics In 2 unrelated Chinese families with autosomal dominant familial episodic pain syndrome-3, Zhang et al. (2013) identified 2 different missense mutations in the SCN11A gene (R225C, 604385.0002; A808G, 604385.0003).
Familial episodic pain syndrome with predominantly upper body involvement is a subtype of familial episodic pain syndrome characterized by episodes of severe debilitating pain mainly affecting shoulders, thorax and arms (occasionally radiating to the abdomen and legs), triggered by fasting, fatigue, cold temperatures or physical exercise, which last for 60-90 min and respond poorly to conventional analgesia.
A number sign (#) is used with this entry because of evidence that familial episodic pain syndrome-1 (FEPS1) is caused by heterozygous mutation in the TRPA1 gene (604775) on chromosome 8q13. ... Description Familial episodic pain syndrome-1 is an autosomal dominant neurologic disorder characterized by onset in infancy of episodic debilitating upper body pain triggered by fasting, cold, and physical stress (summary by Kremeyer et al., 2010). Genetic Heterogeneity of Familial Episodic Pain Syndrome See also FEPS2 (615551), caused by mutation in the SCN10A gene (604427) on chromosome 3p22, and FEPS3 (615552), caused by mutation in the SCN11A gene (604385) on chromosome 3p22. ... Mapping By linkage and haplotype analysis, Kremeyer et al. (2010) mapped the episodic pain syndrome in a large Colombian family to chromosome 8q12-q13. ... Molecular Genetics By linkage analysis followed by candidate gene sequencing in a large Colombian family with episodic pain syndrome, Kremeyer et al. (2010) identified a heterozygous missense mutation in the TRPA1 gene (N855S; 604775.0001).
Familial episodic pain syndrome is a rare, genetic, peripheral neuropathy disorder characterized by recurrent, stereotyped, episodic intense pain, ocurring predominantly in either the upper body or lower limbs in several members of a family, which is triggered or exacerbated by fatigue, cold exposure, fasting, weather changes and/or physical stress or exertion and may or may not diminish with age.
Cataract-congenital heart disease-neural tube defect syndrome is a multiple congenital anomaly syndrome characterized by sacral neural tube defects resulting in tethered cord, atrial and/or ventricular septal heart defects (that are detected in infancy), bilateral, symmetrical hyperopia, rapidly progressive early childhood cataracts, bilateral aphakic glaucoma, and abnormal facial features (low frontal hairline, small ears, short philtrum, prominent, widely spaced central incisors, and micrognathia).
Nail and teeth abnormalities-marginal palmoplantar keratoderma-oral hyperpigmentation syndrome is a rare genetic ectodermal dysplasia syndrome characterized by short stature, nail dystrophy and/or nail loss, oral mucosa and/or tongue hyperpigmentation, dentition abnormalities (delayed teeth eruption, hypodontia, enamel hypoplasia), keratoderma on the margins of the palms and soles and focal hyperkeratosis on the dorsum of the hands and feet.
A number sign (#) is used with this entry because of evidence that ectodermal dysplasia/short stature syndrome (ECTDS) is caused by homozygous mutation in the GRHL2 gene (608576) on chromosome 8q22.
Hemihyperplasia–multiple lipomatosis syndrome Specialty Dermatology Hemihyperplasia–multiple lipomatosis syndrome is a cutaneous condition characterized by multiple lipomas in association with asymmetric (but non-progressive and non-distorting) overgrowth, cutaneous capillary malformations, and thickened plantar skin with prominent creases. [1] See also [ edit ] Involutional lipoatrophy List of cutaneous conditions References [ edit ] ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007).
Hypomyelination-congenital cataract is characterized by the onset of cataract either at birth or in the first two months of life, delayed psychomotor development by the end of the first year of life and moderate intellectual deficit. Epidemiology The syndrome has been described in 10 children from five different families. ... Etiology The progressive neurological degeneration is caused by hypomyelination of the central and peripheral nervous systems. The syndrome is caused by mutations in hyccin, a recently identified nuclear membrane protein encoded by the FAM126A gene (7p15.3).
Hypomyelination and congenital cataract is a very rare disease characterized by cloudy coverings of the eye that are present at birth ( congenital cataracts ) and neurologic impairment that becomes apparent after the first year of life. The neurologic impairment is progressive and presents as ataxia and spasticity. Affected individuals may lose the ability to walk. Signs and symptoms may vary but can include loss of sensation in the hands and feet (peripheral neuropathy), curvature of the spine (scoliosis), difficulty speaking (dysarthria), seizures, and moderate intellectual disability. Hypomyelination and congenital cataract is caused by a change (mutation ) in the FAM126A gene and is inherited in an autosomal recessive manner. Diagnosis of hypomyelination and congenital cataract is based on clinical findings of muscle weakness and cataracts, and a brain MRI that indicates a loss of the myelin surrounding the neurons .
Hypomyelination and congenital cataract is an inherited condition that affects the nervous system and the eyes. This disease is one of a group of genetic disorders called leukoencephalopathies. Leukoencephalopathies involve abnormalities of the brain's white matter. White matter consists of nerve fibers covered by a fatty substance called myelin. Myelin insulates nerve fibers and promotes the rapid transmission of nerve impulses.
A number sign (#) is used with this entry because of evidence that hypomyelinating leukodystrophy-5 (HLD5), also known as hypomyelination and congenital cataract (HCC), is caused by homozygous mutation in the FAM126A gene (610531) on chromosome 7p15. For a general phenotypic description and a discussion of genetic heterogeneity of HLD, see 312080. Clinical Features Zara et al. (2006) identified 10 individuals from 5 families with a disorder characterized by congenital cataract, progressive neurologic impairment, and diffuse myelin deficiency as shown by brain magnetic resonance imaging (MRI). All individuals presented with bilateral cataract at birth or in the first 2 months of life and underwent ocular surgery. Initial psychomotor development was normal. At the end of the first year of life, development was delayed in all individuals.
Summary Clinical characteristics. Hypomyelination and congenital cataract (HCC) is usually characterized by bilateral congenital cataracts and normal psychomotor or only mildly delayed development in the first year of life, followed by slowly progressive neurologic impairment manifest as ataxia, spasticity (brisk tendon reflexes and bilateral extensor plantar responses), and mild-to-moderate cognitive impairment. Dysarthria and truncal hypotonia are observed. Cerebellar signs (truncal titubation and intention tremor) and peripheral neuropathy (muscle weakness and wasting of the legs) are present in the majority of affected individuals. Seizures can occur. Cataracts may be absent in some individuals. Diagnosis/testing. The diagnosis of HCC can be established in individuals with typical clinical findings, characteristic abnormalities on brain MRI, and biallelic pathogenic variants in FAM126A identified by molecular genetic testing. Management. Treatment of manifestations: Cataract extraction usually in the first months of life.
Ring chromosome 3 syndrome is a rare chromosomal anomaly syndrome with a highly variable phenotype principally characterized by pre- and postnatal growth retardation, short stature, developmental delay, mild to severe intellectual disability, microcephaly and mild dysmorphic features (incl. triangular face, dysplastic ears, upslanting palpebral fissures, epicanthic folds, broad nasal bridge, full nasal tip, long philtrum, downturned corners of the mouth, and micro/retrognathia).
Sulzberger–Garbe syndrome Other names Oid-oid disease [1] Specialty Dermatology Sulzberger–Garbe syndrome is a cutaneous condition, a type of therapy resistant nummular eczema . [1] See also [ edit ] Id reaction List of cutaneous conditions References [ edit ] ^ a b Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007).
Clinical Features Although primary anophthalmia has been documented as a manifestation of several mental retardation/congenital anomaly (MCA) syndromes, as reviewed by Leichtman et al. (1994), the nosology of this group of disorders is confusing. Fryns et al. (1995) described an apparently distinct 'anophthalmia-plus' syndrome in sibs. The index patient was a female fetus at 17 weeks' gestation with bilateral anophthalmia, bilateral cleft lip/cleft palate, macrotia with bilateral lateral facial cleft, large open sacral neural tube defect, and uterus unicornis. ... They suggested that this was an example of the Fryns anophthalmia syndrome, which may be an autosomal recessive disorder, although intrauterine environmental factors cannot be excluded. ... Makhoul et al. (2007) stated that this case supported the notion of anophthalmia-plus as a distinct syndrome. Ozalp et al. (2008) reported a 26-week female fetus with bilateral clinical anophthalmia, agenesis of the upper lip and palate, cerebral ventricular dilation, adrenal hypoplasia, and single umbilical artery. ... Ozalp et al. (2008) stated that this was the first report of adrenal hypoplasia in Fryns anophthalmia-plus syndrome. Inheritance Fryns et al. (1995) suggested autosomal recessive inheritance of the disorder.
A very rare multiple congenital anomaly syndrome characterized by the presence of anophthalmia or severe microphthalmia, cleft lip/palate, facial cleft and sacral neural tube defects, along with various additional anomalies including congenital glaucoma, iris coloboma, primary hyperplastic vitreous, hypertelorism, low-set ears, clinodactyly, choanal atresia/stenosis, dysgenesis of sacrum, tethering of spinal cord, syringomyelia, hypoplasia of corpus callosum, cerebral ventriculomegaly and endocrine abnormalities.
Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations is a rare cancer-predisposing syndrome, associated with the D1 subgroup of Fanconi anemia (FA), characterized by progressive bone marrow failure, cardiac, brain, intestinal or skeletal abnormalities and predisposition to various malignancies.
In contrast, the cumulative incidence of hematologic malignancy, defined as the onset of acute leukemia or myelodysplastic syndrome (MDS), by age 40 years is 33%, with no significant difference between the FA complementation groups A (607139), C (227645), and G (614082) (Kutler et al., 2003).
Short stature-pituitary and cerebellar defects-small sella turcica syndrome is characterised by short stature, anterior pituitary hormone deficiency, small sella turcica, and a hypoplastic anterior hypophysis associated with pointed cerebellar tonsils. ... Ectopia of the posterior hypophysis was observed in some patients. The syndrome is transmitted as a dominantly inherited trait and is caused by a germline mutation within the LIM-homeobox transcription factor LHX4 gene (1q25).
A number sign (#) is used with this entry because combined pituitary hormone deficiency-4 (CPHD4) is caused by heterozygous mutation in the LHX4 gene (602146) on chromosome 1q25. For discussion of phenotypic and genetic heterogeneity of combined pituitary hormone deficiency, see CPHD1 (613038). Clinical Features Machinis et al. (2001) reported a French family in which 2 sibs, born of a consanguineous marriage, were found to have combined pituitary hormone deficiency (CPHD) involving growth hormone (GH; 139250), thyrotropin (TSH; 188540) and adrenocorticotropic hormone (ACTH; 202200). MRI imaging showed that both had small sella turcicas, persistent craniopharyngeal canals, hypoplastic anterior hypophyses with associated pointed cerebellar tonsils (Chiari malformation; 118420), and ectopic posterior hypophyses. Their mother was 148 cm tall and had a small sella turcica and a hypoplastic anterior hypophysis associated with a deformation of the cerebellar tonsils.
Nestor-Guillermo progeria syndrome is a rare, genetic, progeroid syndrome characterized by a prematurely aged appearance associated with severe osteolysis (notably on mandible, clavicles, ribs, distal phalanges, and long bones), osteoporosis, generalized lipoatrophy and absence of cardiovascular, atherosclerotic and metabolic complications, presenting a relatively long survival.
A number sign (#) is used with this entry because of evidence that Nestor-Guillermo progeria syndrome is caused by homozygous mutation in the BANF1 gene (603811) on chromosome 11q13. ... Cabanillas et al. (2011) described in detail the 2 patients from unrelated Spanish families who were originally studied by Puente et al. (2011), noting that the phenotype was designated 'Nestor-Guillermo' progeria syndrome using the names of these 2 patients. ... Mapping In a consanguineous Spanish family in which the proband had an atypical progeroid syndrome and was negative for mutations in the LMNA (150330) and ZMPSTE24 (606480) genes, Puente et al. (2011) performed exon enrichment followed by massively parallel sequencing on DNA samples from the proband and both parents under an assumption of an autosomal recessive mode of inheritance. ... Molecular Genetics In a consanguineous Spanish family in which the proband had an atypical progeroid syndrome, Puente et al. (2011) analyzed 4 candidate genes and identified homozygosity for a missense mutation in the BANF1 gene (A12T; 603811.0001) on chromosome 11 that was also found to be present in homozygosity in an unrelated Spanish patient with a nearly identical phenotype.
Fragile X syndrome is a genetic condition involving changes in part of the X chromosome. ... Other signs and symptoms may include symptoms of autism spectrum disorders , seizures, and characteristic physical features. Fragile X syndrome is caused by a change (mutation) in the FMR1 gene and is inherited in an X-linked dominant manner.
Some individuals with fragile X syndrome also meet the diagnostic criteria for autism . ... "Rare FMR1 gene mutations causing fragile X syndrome: A review" . American Journal of Medical Genetics. ... "Further segregation analysis of the fragile X syndrome with special reference to transmitting males". ... "Visualizing carrier status: fragile X syndrome and genetic diagnosis since the 1940s" . ... "Metformin for Treatment of Fragile X Syndrome and Other Neurological Disorders".
Epidemiology Prevalence is estimated at approximately 1/2400-1/6000 although the prevalence may vary, depending on where the screening is carried out in the world. Clinical description Fragile X syndrome (FXS) presents with a variable clinical phenotype. ... Differential diagnosis The differential diagnosis includes other X-linked intellectual deficiencies, Sotos syndrome, microdeletion syndromes (e.g. 22q11.2 deletion syndrome), fetal alcohol syndrome or idiopathic autism.
A Prader-Willi-like subphenotype of the fragile X syndrome was described by de Vries et al. (1993). ... In addition to their summary, over 50 papers on the fragile X syndrome and 18 papers related to other X-linked mental retardation syndromes presented at the conference were published in the American Journal of Medical Genetics. ... MacKenzie et al. (2006) concluded that testing of ectodermally derived tissues may provide improved diagnosis for fragile X syndrome. Coffee et al. (2009) reported the development of an assay for newborn screening of fragile X syndrome. ... With amelogenin PCR used for detecting the presence of a Y chromosome, this assay also detected males with Klinefelter syndrome (47,XXY). Among 64 males with FMR1 methylation, 7 were found to have full-mutation fragile X syndrome and 57 had Klinefelter syndrome. In their study of 36,124 newborn males, Coffee et al. (2009) estimated the incidence of fragile X syndrome to be 1 in 5,161 newborn males, and that of Klinefelter syndrome to be 1 in 633.
MIRAGE syndrome is a condition characterized by Myelodysplasia , Infection, Restriction of growth, Adrenal hypoplasia , Genital problems, and Enteropathy (intestinal problems). ... All patients had low platelet numbers (thrombocytopenia) and/or anemia. MIRAGE syndrome is caused by a change (mutation) in the SAMD9 gene.
A number sign (#) is used with this entry because of evidence that MIRAGE syndrome (MIRAGE) is caused by heterozygous mutation in the SAMD9 gene (610456) on chromosome 7q21. Description MIRAGE syndrome is a form of syndromic adrenal hypoplasia, characterized by myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy. ... Mosaic monosomy 7 (see 252270) was detected in 2 patients, who both developed myelodysplastic syndrome and died from the complication. ... Narumi et al. (2016) proposed the designation MIRAGE syndrome. Molecular Genetics By whole-exome sequencing in 6 Japanese patients with suspected syndromic adrenal hypoplasia, Narumi et al. (2016) identified 3 different heterozygous missense mutations in the SAMD9 gene (610456.0002-610456.0004) in 4 of the patients. ... Genetic analysis in 2 patients with monosomy 7 who developed myelodysplastic syndrome (see 252270) showed loss of the signal derived from the mutant allele, suggesting that there was an expansion of the cells that lost chromosome 7 carrying the mutation.
Rarely, individuals diagnosed with MIRAGE syndrome have the disorder as the result of a variant inherited from a heterozygous parent with no apparent features of MIRAGE syndrome. ... Diagnosis Formal diagnostic criteria for MIRAGE syndrome have not been established. Suggestive Findings MIRAGE syndrome should be suspected in individuals with the following clinical, laboratory, and radiographic features. ... To date, no consensus clinical diagnostic criteria for MIRAGE syndrome are available. In this review, a diagnosis of MIRAGE syndrome is defined as: 46,XY individuals with four or more of the core features; or 46,XX individuals with three or more of the core features. ... A CDKN1C pathogenic variant causing IMAGe syndrome is typically inherited in an autosomal dominant manner; however, only maternal transmission of the pathogenic variant results in IMAGe syndrome. 2. ... Three of the eight individuals with severe MIRAGE syndrome manifestations died of these complications post transplant.
A rare genetic disease characterized by pre- and postnatal growth restriction, developmental delay, adrenal hypoplasia, genital abnormalities (such as microphallus, hypospadias, or cryptorchidism), thrombocytopenia and/or anemia, recurrent severe invasive infections, and enteropathy with chronic diarrhea. Myelodysplastic syndrome and dysmorphic features (including downslanting palpebral fissures, low-set and posteriorly rotated ears, anteverted nares, camptodactyly, and arachnodactyly, among others) may also be observed.
Fetal retinoid syndrome is a characteristic pattern of physical birth defects in a baby that has been exposed to retinoids during pregnancy. ... Some of the birth defects associated with fetal retinoid syndrome may be diagnosed by ultrasound during pregnancy. No treatment exists for fetal retinoid syndrome. Babies born with this condition are treated based on their symptoms.
The designation Verloes-Koulischer oroacral (VKOA) syndrome was suggested in the London dysmorphology database. ... A vascular etiology causing secondary disruption of an area of the maxilla and the tooth buds as well as the limbs was suggested in the previous cases and was compatible with the mechanism sometimes evoked for amniotic bands syndrome (217100), Hanhart syndrome (103300), and the induced limb defects occurring as a complication of chorionic villus sampling (Lipson and Webster, 1993).
Wilf-Miron and Goodman (1987) described a Moslem Arab male infant, with healthy first-cousin parents, who had a seemingly 'new' congenital malformation syndrome that mainly involved the face, thorax, and genitalia. ... Some of the features suggested Aarskog syndrome (305400) and others suggested the Smith-Lemli-Opitz syndrome (270400).
Otofacioosseous-gondadal syndrome was the designation proposed by da-Silva et al. (1997) for a seemingly new syndrome with probable autosomal recessive inheritance, which they observed in 2 sons and possibly a daughter of first-cousin parents. The syndrome consisted of sensorineural deafness, short stature, cryptorchidism, inguinal hernia, brachycephaly, prominent forehead, flat face, downslanting palpebral fissures, low nasal root, hypoplastic alae and round tip to the nose, low-set prominent ears, narrow thorax, genu valgum, wormian bones, fusion of carpal bones, delayed bone age, and congenital clubfoot.
The SATB2-associated syndrome (SAS) is a recently described condition, characterized by developmental delay, intellectual disability with absent or limited language skills, palatal and dental abnormalities, behavioral problems, and unusual facial features. ... The SATB 2 gene is located in chromosome 2q32 (the region designated as q32 on the long ("q") arm of chromosome 2), and many of the features are similar to the " 2q33.1 microdeletion syndrome ". This gene is important for the development of the face, brain and bone. ... The organization UNIQUE has published information about SATB2-associated syndrome .
Genetic counseling. SATB2 -associated syndrome (SAS) is an autosomal dominant disorder. ... Two affected females were described to have Rett syndrome-like phenotypes with limited purposeful hand movements, stereotyped repetitive movements, and bruxism [Lee et al 2016]. ... SATB2 was subsequently identified as the gene associated with this syndrome [FitzPatrick et al 2003]. The designation of SATB2 -associated syndrome (SAS) was recently proposed as a new clinically recognizable syndrome [Döcker et al 2014]. ... SATB2- associated syndrome should be distinguished from other syndromes that include developmental delay and dental abnormalities, such as KBG syndrome. ... Consistent features associated with pathogenic missense, nonsense, and frameshift variants include: long and flat philtrum and thin vermilion of the upper lip [Zarate & Fish 2017; Author, personal observation]. 2. Angelman syndrome is caused by disruption of maternally imprinted UBE3A located within the 15q11.2-q13 Angelman syndrome/Prader-Willi syndrome (AS/PWS) region.