Homozygous 11p15-P14 Deletion Syndrome

A number sign (#) is used with this entry because the disorder is a contiguous gene syndrome caused by homozygous deletion of approximately 122 kilobases on chromosome 11p15-p14, which contains the genes USH1C (605242), ABCC8 (600509), and KCNJ11 (600937).

Bitner-Glindzicz et al. (2000) identified individuals from 2 consanguineous families with severe hyperinsulinism, profound congenital sensorineural deafness, enteropathy, and renal tubular dysfunction. All affected members in 1 family had retinitis pigmentosa; 2 of the 3 affected children in the second family had attenuated electroretinographic studies. The 2 families were not known to be related and came from different countries but shared the same common Arabic surname. The molecular basis of the disorder was found to be a homozygous deletion of 122 kilobases on chromosome 11p15-p14, including part of the ABCC8 and KCNJ11 genes and overlapping with the Usher syndrome IC (276904) and DFNB18 (602092) loci. The ABCC8 and KCNJ11 genes encode components of ATP-sensitive potassium channels and may be mutated in patients with hyperinsulinism. The enteropathy was thought to be explained by partial deletion of the USH1C gene, because immunohistochemistry showed strong positive staining in normal gut. Severe gastrointestinal symptoms included diarrhea with failure to thrive, intractable vomiting, and a feeding disorder, all with foregut dismotility. Small bowel biopsies showed changes indistinguishable from autoimmune enteropathy.