Chromosome 5p13 Duplication Syndrome

A number sign (#) is used with this entry because it represents a contiguous gene syndrome involving duplication of several genes on chromosome 5p13, including NIPBL (608667).

Clinical Features

Yan et al. (2009) identified 5 unrelated patients referred to a medical genetics diagnostic laboratory who were found to have similar microduplications on chromosome 5p13 detected by array comparative genomic hybridization analysis (aCGH). Their ages ranged from 6 months to 30 years, and there were 4 females and 1 male. All patients had developmental delay and mental retardation. About half had low birth weight and became overweight in adulthood. Facial dysmorphism was variable, but some common features included frontal bossing, large or broad forehead, bitemporal narrowing, short or slanted palpebral fissures, short philtrum, high-arched palate, and low-set ears. Individual patients had strabismus, hypo- or hypertelorism, bulbous nose, micrognathia, and low posterior hairline. One patient had large hands and feet, 2 had long fingers, and 1 had scoliosis. One had seizures, 2 had sleep disturbances, and 1 had agenesis of the corpus callosum. One patient had a significant skull deformity with craniosynostosis, turricephaly, and brachycephaly. Yan et al. (2009) distinguished the phenotype from that of Cornelia de Lange syndrome (CDLS1; 122470), which can be caused by mutation in the NIPBL gene.

Cytogenetics

In 5 unrelated patients with mental retardation and dysmorphic facial features, Yan et al. (2009) identified 5 different presumably de novo microduplications of chromosome 5p13. High resolution analysis detected duplications ranging in size from 0.25 to 1.08 Mb. All 5 duplications involved the NIPBL gene, 4 of which duplicated the entire gene; 4 of the duplications included part or all of the FLJ13231 (C5ORF42) gene. The largest duplication contained SLC1A3 (600111), NUP155 (606694), and exons 1 to 9 of the WDR70 gene (617233) in addition to the NIPBL and FLJ13231 genes. Analysis of breakpoint regions suggested several different mechanisms, including nonhomologous end joining (NHEJ), nonallelic homologous recombination (NAHR), and replication fork stalling and template switching (FoSTeS). Yan et al. (2009) suggested that copy number variation can be a common mechanism for genetic diseases.