MedGen

Beckwith-Wiedemann syndrome (BWS) is a growth disorder variably characterized by neonatal hypoglycemia, macrosomia, macroglossia, hemihyperplasia, omphalocele, embryonal tumors (e.g., Wilms tumor, hepatoblastoma, neuroblastoma, and rhabdomyosarcoma), visceromegaly, adrenocortical cytomegaly, renal abnormalities (e.g., medullary dysplasia, nephrocalcinosis, medullary sponge kidney, and nephromegaly), and ear creases/pits. BWS is considered a clinical spectrum, in which affected individuals may have many of these features or may have only one or two clinical features. Early death may occur from complications of prematurity, hypoglycemia, cardiomyopathy, macroglossia, or tumors. However, the previously reported mortality of 20% is likely an overestimate given better recognition of the disorder along with enhanced treatment options. Macroglossia and macrosomia are generally present at birth but may have postnatal onset. Growth rate slows around age seven to eight years. Hemihyperplasia may affect segmental regions of the body or selected organs and tissues. [from GeneReviews]

A group of signs, symptoms, and clinicopathological characteristics that may or may not have a genetic basis and collectively define an abnormal condition. [from NCI]

A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age. [from HPO]

Failure to meet, or late achievement of developmental milestones. [from NCI]

This term applies to a family member who is diagnosed with the same condition as the individual who is the primary focus of investigation (the proband). [from HPO]

No history of any serious disease, including the disease being investigated in the proband. [from HPO]

A cessation of the development of a child in the areas of motor skills, speech and language, cognitive skills, and social and/or emotional skills. [from HPO]

A rare developmental defect during embryogenesis malformation syndrome characterized by congenital, non-communicating hydrocephalus, cerebellar agenesis and absence of the Luschka and Magendie foramina. Patients present with hypotonia, areflexia or hyporeflexia, seizures and/or cyanosis shortly after birth and is fatal in the neonatal period. There have been no further descriptions in the literature since 1973. [from ORDO]

A very rare syndrome associating microcephaly, micrognathia, oculocutaneous albinism, hypoplasia of the distal phalanx of fingers and agenesia of the distal end of the right big toe. It has been described in two siblings. Both brother and sister had psychomotor retardation and died in the course of a respiratory infection. The reported cases suggest that the condition is hereditary, and is transmitted as an autosomal recessive trait. [from SNOMEDCT_US]

A rare genetic myotonic syndrome characterised by childhood onset of progressive and severe myotonia (with generalised muscular hypertrophy and progressive impairment of gait) short stature, skeletal abnormalities (including pectus carinatum, short, wedge-shaped thoracolumbar vertebrae, kyphoscoliosis, genu valgum, irregular femoral epiphyses) and mild to moderate intellectual deficiency. Facial dysmorphism and joint limitation are not associated. There have been no further descriptions in the literature since 1984. [from SNOMEDCT_US]

Microcornea-corectopia-macular hypoplasia syndrome is characterized by microcornea, which may also be accompanied by corectopia and macular hypoplasia. It has been described in three individuals from two successive generations of one family. [from MONDO]

Distal arthrogryposis type 5 is distinguished from other forms of DA by the presence of ocular abnormalities, typically ptosis, ophthalmoplegia, and/or strabismus, in addition to contractures of the skeletal muscles. Some cases have been reported to have pulmonary hypertension as a result of restrictive lung disease (summary by Bamshad et al., 2009). There are 2 syndromes with features overlapping those of DA5 that are also caused by heterozygous mutation in PIEZO2: distal arthrogryposis type 3 (DA3, or Gordon syndrome; 114300) and Marden-Walker syndrome (MWKS; 248700), which are distinguished by the presence of cleft palate and mental retardation, respectively. McMillin et al. (2014) suggested that the 3 disorders might represent variable expressivity of the same condition. For a general phenotypic description and a discussion of genetic heterogeneity of distal arthrogryposis, see DA1A (108120). Genetic Heterogeneity of Distal Arthrogryposis 5 A subtype of DA5 due to mutation in the ECEL1 gene (605896) on chromosome 2q36 has been designated DA5D (615065). See NOMENCLATURE. [from OMIM]

Craniosynostosis-fibular aplasia is an extremely rare genetic disease, reported in only 2 brothers to date, characterized by the combination of craniosynostosis (involving both coronal sutures), congenital absence of the fibula, cryptorchidism, and bilateral simian creases. Intelligence is normal and an autosomal recessive mode of inheritance has been proposed. There have been no further reports in the literature since 1972. [from MONDO]

A rare disorder of sex development characterized by primary amenorrhea and ambiguous external genitalia (enlarged clitoris with marked fusion of the labioscrotal folds) in association with skeletal anomalies (such as hypoplasia of the mandibular condyles and the maxilla, and ulnar dislocation of the radial heads), in the presence of a 46,XX karyotype and regular ovaries, fallopian tubes, and uterus. There have been no further descriptions in the literature since 1972. [from ORDO]

A rare multiple congenital anomalies/dysmorphic syndrome characterized by trigonobrachycephaly, facial dysmorphism (including narrow forehead, upward-slanting palpebral fissures, bulbous nose with slightly bifid tip, macrostomia with thin upper lip, micrognathia), and various acral anomalies, such as broad thumbs, large toes, bulbous fingertips with short nails, joint laxity of the hands and fifth finger clinodactyly. Short stature, hypotonia and severe psychomotor delay are also associated. There have been no further descriptions in the literature since 1991. [from ORDO]

Nathalie syndrome has characteristics of deafness, cataract, muscular atrophy, skeletal abnormalities, growth retardation, underdeveloped secondary sexual characteristics and electrocardiographic abnormalities. It has been described in a Dutch family: in three sisters (one named Nathalie) and their brother. [from SNOMEDCT_US]

A very rare disorder associating pseudopapilloedema (optic disc swelling not secondary to increased intracranial pressure) mixed hearing loss, facial dysmorphism and limb extremity anomalies. Only 4 cases have been reported in the literature from 3 inbred sibships. The affected patients have no intellectual deficit. Transmitted as an autosomal recessive trait. [from SNOMEDCT_US]

Early-onset epilepsy-3 with or without developmental delay (EPEO3) is an autosomal dominant neurologic disorder characterized by the onset of various types of seizures in the first months or years of life. Many patients present with febrile seizures and later develop afebrile seizures. The severity and disease course is highly variable: some affected individuals have global developmental delay or regression with impaired intellectual development, poor or absent speech, and motor delay, whereas others have normal psychomotor development. More severely affected individuals often show additional features, including hypotonia, gait ataxia, nonspecific dysmorphic features, behavioral abnormalities, and variable anomalies on brain imaging (Mattison et al., 2023, Zhao et al., 2023). For a discussion of genetic heterogeneity of EPEO, see 617290. [from OMIM]

Early-onset epilepsy-2 with or without developmental delay (EPEO2) is an autosomal dominant neurologic disorder characterized by the onset of generalized tonic-clonic seizures in the first days, months, or years of life. The severity is highly variable: some patients have normal psychomotor development and normal brain imaging, whereas others may show developmental delay associated with abnormalities on brain imaging (summary by Yu et al., 2019). For a discussion of genetic heterogeneity of EPEO, see 617290. [from OMIM]