AP1S2 defects cause an X-linked neurodevelopmental disorder that presents with both non-syndromic and syndromic intellectual disabilities. The early onset of global developmental delay leads to moderate to severe intellectual disability and is accompanied by a characteristic behavioral profile, including dramatic early onset self-injurious behaviors reminiscent of those observed in Lesch-Nyhan disease, as well as autistic-like conduct. Hypotonia is typically reported early in infancy, predicting global developmental delay. Epilepsy occurs later in some patients, often manifesting in adulthood.
Syndromic presentations may include facial dysmorphisms, ligamentous laxity, mild muscular hypotrophy, and hypotonia, which are evident during childhood, along with microcephaly or macrocephaly, hydrocephalus, Dandy-Walker syndrome, periventricular nodular heterotopia, cerebellar defects, striatal calcification, or basal ganglia iron deposition. Some of these features have been collectively described as Fried and Pettigrew syndromes. The disease results in a stable, severely disabling condition in adulthood.
AP1S2