Chromosome 15q14 Deletion Syndrome

A number sign (#) is used with this entry because it represents a contiguous gene deletion syndrome on chromosome 15q14. The deleted region includes the MEIS2 gene (601740).

Clinical Features

Erdogan et al. (2007) reported a 4-year-old girl who presented at birth with cleft palate, atrial septal defect, and hypotonia. She subsequently showed delayed psychomotor development and moderate mental retardation. Mild dysmorphic features included low-set posteriorly rotated ears, short philtrum, and pointed chin. Array CGH identified a de novo heterozygous 5.3-Mb interstitial deletion of chromosome 15q14 that included the MEIS2 gene (601740).

Johansson et al. (2014) reported 5 children, including 2 sibs, with heterozygous deletions involving chromosome 15q14. Two sisters shared a 0.6-Mb deletion that was maternally inherited, whereas the deletions in the other 3 patients occurred de novo; the latter 3 deletions ranged in size from 1.0 to 4.8 Mb. All patients had delayed motor development, and all but 1 had delayed intellectual development that was generally mild. The 2 sisters and 1 additional child had cleft palate; 1 of the sisters and 2 additional patients had ventricular septal defects. Only the patient with the 4.8-Mb deletion had clearly dysmorphic features, including lower-set ears, bulbous nose with wide and low columella, and everted upper lip. The other patients shared a high forehead, finely arched eyebrows, and mildly shortened philtrum with tented upper lip. The deleted region in all cases included the MEIS2 gene. Johansson et al. (2014) also reported a mother and her 3 children who had a heterozygous 58-kb duplication within the MEIS2 gene that was predicted to result in a frameshift and premature termination. All 4 family members had cleft palate, mildly delayed motor development, and mild intellectual disability (see 601740.0001). The findings in all 9 patients suggested that cleft palate is associated with haploinsufficiency for the MEIS2 gene.

Conte et al. (2016) performed a bioinformatics and statistical analysis of copy number variations (CNV) associated with cleft lip/palate by examining 2 large CNV databases. After filtration, 5 of 312 patients were found to carry deletions involving the MEIS2 gene, suggesting that MEIS2 is a candidate gene for orofacial clefting. However, a large number of individuals (approximately 140) from a control database were also found to carry deletions involving the MEIS2 gene, and these deletions tended to disrupt the promoter region.