Chromosome 2q31.1 Duplication Syndrome

A number sign (#) is used with this entry because it represents a contiguous gene syndrome caused by duplication at chromosome 2q31.1 (chr2:176.7-177.7 Mb, NCBI36).

Clinical Features

Cho et al. (2010) described a 3-generation Korean family segregating autosomal dominant mesomelic dysplasia and a 2q31.1 duplication (see MOLECULAR GENETICS). A brother and sister and their mother and maternal grandmother all had short stature and distinctively short forearms, although they displayed some clinical variability: the maternal grandmother had relatively mild forearm shortening and less severe short stature, and had normal-looking, well-functioning hands, whereas the mother had complex hand anomalies, including 5 fingers and a hypoplastic triphalangeal thumb on the left hand and 5 fingers without a thumb on the right hand. The mesomelic pattern was not grossly evident in the lower extremities, but radiologic measurements showed relative shortening of the tibia and fibula compared to the femur. Feet and ankles were normal in all affected family members, except for the brother, who was born with right congenital clubfoot. No abnormality was observed in the spine. Cho et al. (2010) noted that the phenotype in this family resembled that of the Kantaputra type of mesomelic dysplasia (MMDK; 156232) in terms of marked radial and ulnar shortening associated with relatively mild tibial or fibular shortening; however, affected members of the Korean family did not have calcaneofibular fusion, carpotarsal synostoses, or tibiofibular synostosis, features that are characteristically seen in MMDK.

Ghoumid et al. (2011) reported a father and his 6-year-old daughter with a 2q31.1 duplication who had pendular nystagmus and bilateral cutaneous syndactyly of the third and fourth fingers with normal radiologic findings. Ophthalmologic and neurologic examinations were also normal.

Mapping

In a 3-generation Korean family segregating autosomal dominant mesomelic dysplasia, Cho et al. (2010) performed genomewide copy number variation analysis and found DNA amplifications of a 1.0-Mb region at chromosome 2q31.1 (chr2:176,659,417-177,679,909, NCBI36) in affected family members that was not found in unaffected individuals. The microduplicated region contains 9 HOXD genes (see, e.g., HOXD3, 142980) and the MTX2 gene (608555). Real-time PCR confirmed the heterozygous microduplication and indicated that the maternal grandmother, who had a milder phenotype, was most likely a somatic mosaic for the microduplication. Cho et al. (2010) noted that the Kantaputra type of mesomelic dysplasia had also been mapped to a chromosomal region comprising 2q31.1, and suggested that MMDK and the condition seen in the Korean family might be allelic.

In a father and daughter with pendular nystagmus and bilateral cutaneous syndactyly of the third and fourth fingers, Ghoumid et al. (2011) identified a 3.8-Mb duplication at 2q31.1-q31.2, which involved 27 genes including the entire HOXD cluster.