Inflammatory Skin And Bowel Disease, Neonatal, 1

A number sign (#) is used with this entry because of evidence that neonatal inflammatory skin and bowel disease-1 (NISBD1) is caused by homozygous mutation in the ADAM17 gene (603639) on chromosome 2p25. One such family has been reported.

Genetic Heterogeneity of Neonatal Inflammatory Skin and Bowel Disease

Also see NISBD2 (616069), caused by mutation in the EGFR gene (131550) on chromosome 7p11.

Clinical Features

Blaydon et al. (2011) reported a brother and sister, born of first-cousin parents of Lebanese origin, with neonatal inflammatory skin and bowel disease. The skin lesions, which developed on the second day of life, involved perioral and perianal erythema with fissuring and a generalized pustular rash that developed into psoriasiform erythroderma, with flares of erythema, scaling, and widespread pustules. The skin was prone to infection with Staphylococcus aureus in childhood, resulting in recurrent blepharitis and otitis externa. Diarrhea developed in the first week of life and was predominantly bloody with malabsorptive characteristics, worsening in parallel with increases in the severity of the skin disease and exacerbated by intercurrent gastrointestinal infections. The sibs' hair was short or broken, and their eyelashes and eyebrows were wiry and disorganized. They had thickened nails, with frequent paronychia caused by candida and pseudomonas infections. The sister died at 12 years of age from fulminant parvovirus B19-associated myocarditis, and on subsequent evaluation, the brother was found to have left ventricular dilation.

Molecular Genetics

In an affected brother and sister from a consanguineous family of Lebanese origin with neonatal inflammatory skin and bowel disease, Blaydon et al. (2011) performed SNP-homozygosity mapping followed by targeted next-generation sequencing and identified homozygosity for a 4-bp deletion in the ADAM17 gene (603639.0001). Their unaffected parents were heterozygous for the deletion, which was not found in their unaffected brother.