Clinical Characteristics

Homozygous pathogenic variants in the HERC1 gene are associated with syndromic intellectual disability. The following are the clinical features of this condition:
• Macrocephaly. Individuals with HERC1 mutations are reported to have macrocephaly of prenatal onset which persists into adulthood for some and normalizes with age for others.
• Facial dysmorphism with prominent forehead, long face, prognathism, hypertelorism, sparse and flared eyebrows. Prominent eyes, abnormal slant of palpebral fissures and large ears reported in some individuals.
• Moderate-severe intellectual disability with speech impairment or absent speech.
• Hypotonia.
• Skeletal abnormalities like joint laxity, kyphosis, scoliosis, lordosis, elongated limbs, large hands, arachnodactyly, large and flat feet.
• Seizures in some patients.
• Behavioural abnormalities including autistic features and hyperactivity.
• Structural brain abnormalities, such as megalencephaly, ventriculomegaly, thick corpus callosum, cortical atrophy, cerebellar atrophy in some patients.
• Micropenis reported in one individual.
• Length and weight >+2SD at birth, usually normalises with age.
• Normal bone age.