Deletions in chromosome 6p22.3-p24.3, including ATXN1, are associated with developmental delay and autism spectrum disorders

Deletions involving the distal part of the short arm of chromosome 6 are relatively rare. Terminal deletions of 6p24-pter have been associated with developmental delay, brain malformations (including Dandy-Walker malformation), anterior eye chamber abnormalities, hearing loss, ear abnormalities, micrognathia, and heart defects [1-6]. Patients with larger sized deletions of 6p23-pter also presented with microcephaly, genital anomalies, language impairment, and delayed motor development [1,3,5,7-14]. The identified ocular developmental abnormalities are caused by deficiency of the dosage sensitive FOXC1 gene (MIM 01090) [15-20]. In addition, deletions and duplications involving FOXC1 have been shown recently to be responsible for Dandy-Walker malformation [21].Interstitial deletions of 6p22-p24 have been reported even less often and are generally associated with psychomotor and growth delay, hypotonia as well as several congenital abnormalities, including hydrocephalus, microcephaly, structural eye abnormalities, hypertelorism, low set and rotated ears, nasal anomalies, micrognathia, palatal abnormalities, short folded neck, defects of heart, kidney, and feet, abnormal genitalia, and abnormal fingers with hypoplastic nails [4,5,13,22-26].Here, we describe six individuals, five of whom have overlapping interstitial deletions in chromosome 6p22.3-p24.3 encompassing ATXN1. The majority of patients had neurological or behavioral abnormalities, including developmental and speech delay, autism spectrum disorders (ASDs), attention deficit hyperactivity disorder (ADHD), repetitive behaviors, and various dysmorphic features.This 15-year-old male proband was enrolled in the South Carolina Autism Project (SCAP) study at the J.C. Self Research Institute of Human Genetics at the Greenwood Genetics Center in Greenwood, South Carolina. He was the second child of healthy parents. The pregnancy and delivery were uneventful. He was developmentally delayed, used a few words until 3 year