Widespread aplasia cutis congenita in sibs with PLEC1 and ITGB4 variants

• Published in: American journal of medical genetics. Part A Vol. 179; no. 8; pp. 1547 - 1555
• Main Authors: Kariminejad, Ariana, Vahidnezhad, Hassan, Ghaderi‐Sohi, Siavash, Ghannadan, Ali R., Youssefian, Leila, Parsimehr, Elham, Faraji Zonooz, Mehrshid, Kariminejad, Mohammad H., Uitto, Jouni, Najmabadi, Hossein, Hennekam, Raoul C.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.08.2019; Wiley Subscription Services, Inc
• Subjects: Aplasia; aplasia cutis congenital; autosomal recessive; ITGB4; Nose; Offspring; Physical characteristics; PLEC1; Skin; total skin aplasia; aplasia cutis congenital; total skin aplasia; ITGB4; PLEC1; autosomal recessive
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.61260

Aplasia cutis congenita (ACC) is a heterogeneous group of disorders characterized by localized or widespread absence of skin. ACC can occur isolated or as part of a syndrome. Here we report two consanguineous families, each with two affected offspring. Affected individuals showed widespread ACC while the skin in between had a normal appearance. Ears and nose of the four patients were underdeveloped, otherwise there were no unusual physical characteristics and no internal organ anomalies. “Whole” exome sequencing (WES) of the mother of Family 1 yielded a pathogenic heterozygote variant in ITGB4. The father and healthy offspring were heterozygous for the same variant. WES of the mother of Family 2 yielded a variant in PLEC1. The father and grandmother, who had a history of two offspring with fatal ACC, were heterozygous for the same variant. PLEC1 and ITGB4 have both been previously been reported in association with ACC. We compare findings in earlier reported individuals with variants in ITGB4 and PLEC1, and provide a short summary of other entities going along with ACC.