SMARCE1, a rare cause of Coffin-Siris Syndrome: Clinical description of three additional cases

Abstract

Coffin-Siris syndrome (CSS, MIM 135900), is a well-described, multiple congenital anomaly syndrome characterized by coarse facial features, hypertrichosis, sparse scalp hair, and hypo/aplastic digital nails and phalanges, typically of the 5th digits. Mutations in the BAF (SWI/SNF)-complex subunits (SMARCA4, SMARCE1, SMARCB1, SMARCA2, ARID1B, and ARID1A) have been shown to cause not only CSS, but also related disorders including Nicolaides-Baraitser (MIM 601358) syndrome and ARID1B-intellectual disability syndrome (MIM 614562). At least 200 individuals with CSS have been found to have a mutation in the BAF pathway. However, to date, only three individuals with CSS have been reported to have pathogenic variants in SMARCE1. We report here three additional individuals with clinical features consistent with CSS and alterations in SMARCE1, one of which is novel. The probands all exhibited dysmorphic facial features, moderate developmental and cognitive delay, poor growth, and hypoplastic digital nails/phalanges, including digits not typically affected in the other genes associated with CSS. Two of the three probands had a variety of different organ system anomalies, including cardiac disease, genitourinary abnormalities, feeding difficulties, and vision abnormalities. The 3rd proband has not had further investigative studies. Although an increasing number of individuals are being diagnosed with disorders in the BAF pathway, SMARCE1 is the least common of these genes. This report doubles the number of probands with these mutations, and allows for better phenotypic information of this rare syndrome. © 2016 Wiley Periodicals, Inc.

Keywords: BAF-complex; Coffin-Siris syndrome; SMARCE1; exome sequencing.

FIG. 1

Patient 1 at 19 months of age. (A) Eyelashes and eyebrows were present but sparseness of the scalp hair was also appreciated. (B and C) Note hypoplastic 5th toenails as well as midline split on the right hallux toenail. [Color figure can be seen in the online version of this article, available at http://wileyonlinelibrary.com/journal/ajmga].

FIG. 2

Patient 2 at 1 year of age. (A) She displays a high anterior hairline, sparse scalp hair, long eyelashes, and coarse facial features with thick lips. (B) Hypoplastic nails to the great and 5th toes. (C) Profile demonstrates low-set ears and sparse scalp hair. [Color figure can be seen in the online version of this article, available at http://wileyonlinelibrary.com/journal/ajmga].

FIG. 3

Patient 3 at 8 years of age. (A) patient was noted to have straight eyebrows with downslanting palpebral fissures, a bulbous nasal tip, high-arched palate, low anterior hairline, trigonocephaly, and low-set ears. (B) sparse scalp hair. (C) Right hand demonstrating absent second digit nail. [Color figure can be seen in the online version of this article, available at http://wileyonlinelibrary.com/journal/ajmga].