MedGen

ESCO2 spectrum disorder is characterized by mild-to-severe prenatal growth restriction, limb malformations (which can include bilateral symmetric tetraphocomelia or hypomelia caused by mesomelic shortening), hand anomalies (including oligodactyly, thumb aplasia or hypoplasia, and syndactyly), elbow and knee flexion contractures (involving elbows, wrists, knees, ankles, and feet [talipes equinovarus]), and craniofacial abnormalities (which can include bilateral cleft lip and/or cleft palate, micrognathia, widely spaced eyes, exophthalmos, downslanted palpebral fissures, malar flattening, and underdeveloped ala nasi), ear malformation, and corneal opacities. Intellectual disability (ranging from mild to severe) is common. Early mortality is common among severely affected pregnancies and newborns; mildly affected individuals may survive to adulthood. [from GeneReviews]

Trichorhinophalangeal syndrome (TRPS) comprises TRPS I (caused by a heterozygous pathogenic variant in TRPS1) and TRPS II (caused by a contiguous gene deletion of TRPS1, RAD21, and EXT1). Both TRPS types are characterized by distinctive facial features (large nose with broad nasal ridge and tip and underdeveloped alae; thick and broad medial eyebrows; long philtrum; thin vermilion of the upper lip; and large prominent ears); ectodermal features (fine, sparse, depigmented, and slow-growing hair and dystrophic nails); and skeletal findings (short stature, brachydactyly with ulnar or radial deviation of the fingers, short feet, and early, marked hip dysplasia). TRPS II is additionally characterized by multiple osteochondromas and an increased risk of mild-to-moderate intellectual disability. [from GeneReviews]

Witteveen-Kolk syndrome (WITKOS) is an autosomal dominant disorder with characteristic distinctive facial features, microcephaly, short stature, and mildly impaired intellectual development with delayed cognitive and motor development and subtle anomalies on MRI-brain imaging (summary by Balasubramanian et al., 2021). [from OMIM]

Uruguay faciocardiomusculoskeletal syndrome (FCMSU) is an X-linked disorder in which affected males have a distinctive facial appearance, muscular hypertrophy, and cardiac ventricular hypertrophy leading to premature death. Additional features include large, broad, and deformed hands and feet, congenital hip dislocation, and scoliosis (summary by Xue et al., 2016). [from OMIM]

WDR26-related intellectual disability (ID) is characterized by developmental delay / intellectual disability, characteristic facial features, hypotonia, epilepsy, and infant feeding difficulties. To date 15 individuals, ages 24 months to 34 years, have been reported. Developmental delay is present in all individuals and ranges from mild to severe. All individuals have delayed speech. Although some begin to develop speech in the second year, others have remained nonverbal. Seizures, present in all affected individuals reported to date, can be febrile or non-febrile (tonic-clonic, absence, rolandic seizures); most seizures are self limited or respond well to standard treatment. Affected individuals are generally described as happy and socially engaging; several have stereotypies / autistic features (repetitive or rocking behavior, abnormal hand movements or posturing, and at times self-stimulation). [from GeneReviews]

Autosomal dominant intellectual developmental disorder-60 with seizures is characterized by global developmental delay apparent in infancy, followed by onset of seizures in the first years of life. Patients have delayed walking, an ataxic gait, and moderately to severely impaired intellectual development with poor speech (summary by Helbig et al., 2019). [from OMIM]

A rare genetic multiple congenital anomalies/dysmorphic syndrome characterised by the association of severe intellectual disability, strabismus, and anterior maxillary protrusion with vertical maxillary excess, open bite, and prominent crowded teeth. Mild cochlear hearing loss has been reported in addition. [from SNOMEDCT_US]

Neurodevelopmental disorder with progressive movement abnormalities, cognitive decline, and brain abnormalities (NEDMCB) is an autosomal recessive disorder characterized by global developmental delay and developmental regression resulting in variably impaired intellectual development with poor or absent speech, difficulty walking or inability to walk, and various movement abnormalities, including spasticity, hypertonia, dystonia, tremor, and myoclonus. Affected individuals usually show poor overall growth, often with microcephaly, hypotonia, limb contractures, and cataracts. Most have progressive brain imaging abnormalities, including enlarged ventricles, white matter loss, and cerebellar atrophy. A subset of patients have combined malonic and methylmalonic aciduria (CMAMMA), although this is not a reliable biomarker (Ortigoza-Escobar et al., 2024). [from OMIM]

Neurodevelopmental disorder with poor growth, large ears, and dysmorphic facies (NEDGEF) is an autosomal recessive disorder characterized by these features as well as hypotonia and global developmental delay with impaired intellectual development. The severity is variable, even within families. Death in early childhood has been reported in 1 family (Alsaif et al., 2021). [from OMIM]

Abnormally increased dimension of the maxilla, especially relative to the mandible, resulting in a malocclusion or malalignment between the upper and lower teeth or in anterior positioning of the nasal base, increased convexity of the face, increased nasolabial angle, or increased width (transverse dimension of the maxilla. [from HPO]