Chromosome 17q21.31 Duplication Syndrome

A number sign (#) is used with this entry because it represents a contiguous gene duplication syndrome.

A locus for autism-7 (AUTS7; 610676) has been mapped to chromosome 17q21. See also chromosome 17q21.31 deletion syndrome (610443).

Clinical Features

Kirchhoff et al. (2007) reported a 10-year-old Moroccan girl with severe psychomotor delay who was found to have a de novo duplication at the chromosome 17q21.31 deletion syndrome locus. She had facial dysmorphism, short stature, microcephaly, abnormal digits, and hirsutism. Brain imaging was normal. She walked independently at age 5 years and only said a few words at age 10 years. She was a happy girl and was often singing and dancing. Her general health was good, but she had atopic dermatitis and constipation. Facial features included a short nose with prominent nasal tip and columella, smooth philtrum, small mouth, and micrognathia. The ears were normally positioned, but with unfolded helixes. She had a high-arched palate and protruding upper incisors. The thumbs were short and broad, and there was terminal broadening of the remaining fingers; her feet were broad with a long first toe.

Grisart et al. (2009) reported 4 unrelated individuals with different duplications of chromosome 17q21.31 identified by array-comparative genomic hybridization (CGH) analysis of 13,070 patients with mental retardation and congenital malformations. The patients ranged in age from 6 to 18 years. Although all had some degree of psychomotor retardation and poor social interaction and communication difficulties reminiscent of autism spectrum disorder (ASD; 209850), specific features were more variable. Two had hypotonia, 2 had hyperactivity, 2 had aggressive behavior, and 1 had obsessive behavior. Two had poor motor skills, and 2 showed tiptoe walking. Dysmorphic features were variable and included synophrys (2), dysplastic ears (3), upturned nose (2), flat midface (2), prominent incisor (2), fifth finger clinodactyly (2), and syndactyly (2). One had hirsutism, and another had a low posterior hairline. The 18-year-old showed hypogonadism.

Cytogenetics

In a Moroccan girl with severe psychomotor delay and dysmorphic features, Kirchhoff et al. (2007) identified a de novo 485-kb duplication at chromosome 17q21.31 using array CGH analysis. The duplication was paternally inherited and derived from meiotic recombination of paternal H1 and H2 haplotypes in the 17q21.31 chromosomal region (see MAPT; 157140). The duplication was believed to result from nonallelic homologous recombination (NAHR) between the 2 alleles.

Grisart et al. (2009) reported 4 unrelated individuals with duplications of chromosome 17q21.31 identified by array CGH analysis. The duplication breakpoints were different but were ascertained by different microarray technologies. The size of the duplications ranged from 585 to 763 kb. Three patients with complete testing available had de novo duplications, all of which occurred on the maternal chromosome. Microsatellite and haplotype analysis showed that the duplication occurred by interchromosomal rearrangement between H1 and H2 haplotypes in 2 patients and by interchromatid rearrangement between 2 H2 haplotypes in 1 patient. Grisart et al. (2009) suggested that the duplications likely resulted from NAHR.