Congenital diaphragmatic hernia as a prominent feature of a SPECC1L-related syndrome.

TitleCongenital diaphragmatic hernia as a prominent feature of a SPECC1L-related syndrome.
Publication TypeJournal Article
Year of Publication2020
AuthorsK Wild, T, Gordon, T, Bhoj, EJ, Du, H, Jhangiani, SN, Posey, JE, Lupski, JR, Scott, DA, Zackai, EH
JournalAm J Med Genet A
Date Published2020 Sep 21
ISSN1552-4833
Abstract

Congenital diaphragmatic hernias (CDH) confer substantial morbidity and mortality. Genetic defects, including chromosomal anomalies, copy number variants, and sequence variants are identified in ~30% of patients with CDH. A genetic etiology is not yet found in 70% of patients, however there is a growing number of genetic syndromes and single gene disorders associated with CDH. While there have been two reported individuals with X-linked Opitz G/BBB syndrome with MID1 mutations who have CDH as an associated feature, CDH appears to be a much more prominent feature of a SPECC1L-related autosomal dominant Opitz G/BBB syndrome. Features unique to autosomal dominant Opitz G/BBB syndrome include branchial fistulae, omphalocele, and a bicornuate uterus. Here we present one new individual and five previously reported individuals with CDH found to have SPECC1L mutations. These cases provide strong evidence that SPECC1L is a bona fide CDH gene. We conclude that a SPECC1L-related Opitz G/BBB syndrome should be considered in any patient with CDH who has additional features of hypertelorism, a prominent forehead, a broad nasal bridge, anteverted nares, cleft lip/palate, branchial fistulae, omphalocele, and/or bicornuate uterus.

DOI10.1002/ajmg.a.61878
Alternate JournalAm. J. Med. Genet. A
PubMed ID32954677
Grant ListR01HD064667 / / Eunice Kennedy Shriver National Institute of Child Health and Human Development /
R01HD098458 / / Eunice Kennedy Shriver National Institute of Child Health and Human Development /
K08 HG008986, UM1 HG006542 / HG / NHGRI NIH HHS / United States