Chromosome 4q32.1-Q32.2 Triplication Syndrome

A number sign (#) is used with this entry because it represents a contiguous gene triplication syndrome (chr4:157.35-161.61).

Clinical Features

Wang et al. (2009) reported a mother and her 3 sons who all had a 4.3-Mb triplication of chromosome 4q32.1-q32.2 associated with delayed psychomotor development and variable mental retardation. Common dysmorphic features included macrocephaly, a long midface, hypoplastic zygoma, wide nasal bridge, short nose and underdeveloped columella, downslanting and small palpebral fissures, and small, low-set and squared-off ears. Two of the 3 sons had Hirschsprung disease (see 142623), and the third son had constipation at birth. As a child, the mother was diagnosed with infantile autism, epilepsy, significant developmental delay, learning disabilities, and speech abnormalities. Seizures appeared to be under control as an adult. Physical examination showed myopathic facies, small ears, downslanting and small palpebral fissures, microretrognathia, and long, tapered fingers. She completed grade 13 in a special education setting. Her sons had similar facial features and delayed development; 1 was diagnosed with autism spectrum disorder (209850).

Cytogenetics

In a mother and 3 sons with delayed development, dysmorphic facial features, and variable expression of Hirschsprung disease, Wang et al. (2009) identified a 4.3-Mb triplication at chromosome 4q32.1-q32.2. The authors noted that a locus associated with the development of Hirschsprung disease has been mapped to this region (HSCR9; 611644).