Congenital diaphragmatic hernia as a prominent feature of a SPECC1L‐related syndrome. Issue 12 (21st September 2020)

• Record Type: Journal Article
• Authors: Wild, K. Taylor; Gordon, Tia; Bhoj, Elizabeth J.; Du, Haowei; Jhangiani, Shalini N.; Posey, Jennifer E.; Lupski, James R.; Scott, Daryl A.; Zackai, Elaine H.
• Is Part Of: American journal of medical genetics. Volume 182:Issue 12(2020)
• Page Start: 2919
• Page End: 2925
• Publication Date: 2020-09-21
• Subjects: congenital diaphragmatic hernia (CDH) -- MID1 -- Opitz G/BBB syndrome -- SPECC1L‐related syndrome; Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.61878
• Languages: English
• ISSNs: 1552-4825

Abstract

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.