Heterozygous mutations in SMARCA4 have been reported in 12 patients with Coffin-Siris syndrome [Tsurusaki et al., 2012, 2014b; Kosho et al., 2013; Santen et al., 2013].

Clinical characteristics

About half of the patients have severe developmental delay or ID, and occasionally (20–30%) speak no words.

Growth impairment is mild prenatally and mild‐to‐moderate postnatally, and difficulty in sucking/feeding is almost always observed.

Typical facial features include sparse scalp hair, thick eyebrows, long eyelashes, ptosis, flat nasal bridge, short philtrum, and thick lower lip vermilion. Facial coarseness is evident and a pointed chin in older ages is noted.

Hypertrichosis is always observed.

Patients always have hypoplastic fifth fingers or toes and hypoplastic fifth fingernails or toenails, and sometimes (40–50%) have hypoplastic other fingernails or toenails.

Internal organs are impaired in most.

Patients usually have hypotonia, structural CNS abnormalities, and behavioural abnormalities.

Molecular characteristics

The mutations, all non‐truncating (missense or in‐frame deletions), are predicted to exert dominant‐negative or gain‐of‐function effects.