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

Am J Med Genet A

. 2020 Sep 21. doi: 10.1002/ajmg.a.61878. Online ahead of print.

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

K Taylor Wild 1 2Tia Gordon 3 4Elizabeth J Bhoj 1 5Haowei Du 3Shalini N Jhangiani 6Jennifer E Posey 3James R Lupski 3 6 7 8Daryl A Scott 3 8 9Elaine H Zackai 1Affiliations expand


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.

Keywords: MID1; Opitz G/BBB syndrome; SPECC1L-related syndrome; congenital diaphragmatic hernia (CDH).

© 2020 Wiley Periodicals LLC.

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