Major clinical features
• Characteristic facial features include full cheeks, a high hairline, bitemporal narrowing, deep-set eyes, down slanting palpebral fissures, hypertelorism, high frontal hairline, frontal bossing, and deep-set eyes
• Hypotonia in infancy
• Motor delay
• Intellectual disability is reported in all cases but severity varies from mild to profound
• Autism spectrum disorder are frequent but may be under estimated because many case have not undergone the full evaluation for ASD
• Seizure has been reported but not common
• Other behavioural issues including anxiety disorder, attention-deficit/hyperactivity disorder, aggression, sleep disturbances
• Ectodermal abnormalities including thin and brittle as well as slow growing hair, and thin nails
• Abnormal dentition including crumbling teeth and enamel hypoplasia
• Cryptorchidism
• Congenital heart defects
• Hypothyroidism
• Premature aging in old patients
• Skeletal anomalies, including craniosynostosis, kypho/scoliosis, lower limb asymmetry, distal brachydactyly, camptodactyly, overlapping toes, and multiple fractures
Prevalence: unknown
Inheritance: H1-4 syndrome is an autosomal dominant disorder, typically caused by a de novo pathogenic variant. To date, most are caused by de novo H1-4 pathogenic variants.
H1-4