Coffin-Siris syndrome: Review and presentation of new cases from a questionnaire study

Abstract

To clarify the phenotypic variability of Coffin-Siris syndrome, we present a review of the literature and 18 new cases. We performed a questionnaire study of patients ascertained through an international support group. Information on their sibs was available for comparison. The most frequent findings include some degree of mental retardation or developmental delay, "coarse" facial appearance, feeding difficulties, frequent infections, and hypoplastic to absent fifth fingernails and fifth distal phalanges. We discuss the key manifestations for diagnosis, medical and developmental implications, and possible pathogenesis.

Coffin-Siris syndrome with café-au-lait spots, obesity and hyperinsulinism caused by a mutation in the <i>ARID1B</i> gene

“…The mutation was confirmed by Sanger sequencing. We hypertrichosis, aplasia or hypoplasia of the distal phalanx or nail of the fifth digit and agenesis of the corpus callosum (2). This definition was based completely on clinical findings and was made before the molecular basis of CSS was well known.…”

“…Coffin-Siris syndrome (CSS, MIM 135900) is characterized by mild-to-moderate intellectual disability (ID), severe speech impairment, coarse facial features, hypertrichosis, hypoplastic or absent fifth fingernails or toenails and agenesis of the corpus callosum (1,2).…”

A rare cause of syndromic hypotrichosis: Nicolaides-Baraitser syndrome

“…In this setting, differential diagnosis of NBS mainly includes Coffin-Siris, tricho-rhino-phalangeal, and cardio-facio-cutaneous syndromes, and trichothiodystrophy (Table II). [7][8][9][10] An accurate evaluation of the clinical history, and of the facial, heart, and hand anomalies, drives the clinician toward the most probable diagnosis. However, examination of the skin and adnexa (especially, hair and nails) is of utmost importance to confirm the initial suspicion (Table II).…”

Coffin–Siris Syndrome with obesity, macrocephaly, hepatomegaly and hyperinsulinism caused by a mutation in the ARID1B gene

“…Proposed minimal criteria for the clinical diagnosis of CSS are developmental or cognitive delay, which may range from mild to severe, distinctive facial features that coarsen over time, hypertrichosis and hypoplastic or absent fifth distal phalanx or nail. 1,2 Also, other ectodermal, constitutional and/or organ-related features may be present. 3 CSS is now classified as a BAF (also known as SWI/SNF) complex disorder, 4 as several syndrome-related genes that encode subunits of the BAF complex -ARID1A, ARID1B, SMARCA4, SMARCB1, SMARCA2 and SMARCE1 -have been identified.…”