The Coffin–Siris syndrome (CSS) is a multiple congenital anomalies/mental retardation syndrome (MCA/MR) of hitherto unknown etiology (Coffin & Siris, 1970). Cardinal features are mild to moderate mental and developmental retardation, a characteristic coarse-appearing face, scalp hypotrichosis, diffuse hirsutism, postnatal growth retardation and lax joints. The most characteristic finding is hypoplasia or absence of the fifth finger and/or toe, although other fingers or toes may be involved as well. Other features are less common: congenital heart defects, central nervous system abnormalities, urogenital anomalies, dislocated radial head, coxa valga. Feeding difficulties and respiratory problems are common in infancy (Coffin & Siris, 1970; Weiswasser et al., 1973; Sylvester et al., 1976; Carey & Hall, 1978; Gellis & Feingold, 1978; Tunnessen et al., 1978; Schinzel, 1979; Ueda et al., 1980; Qazi et al., 1990). We review the data on 51 patients reported in the literature so far, with special attention to the 13 patients with Coffin–Siris syndrome examined at the Center of Human Genetics of Leuven in the period 1976–1998.
The diagnosis of Coffin–Siris syndrome in an individual patient is based on the combination of typical clinical signs and symptoms, i.e., developmental delay, postnatal growth deficiency, a typical constellation of craniofacial anomalies (Fig. 39.1(a), (b)) with coarse-appearing face, full lips, large mouth, scalp hypotrichosis with contrasting frontal and facial hirsutism, eyebrow and eyelash hypertrichosis, diffuse hirsutism and, most typically, hypoplastic to absent fifth finger nails and phalanges (Fig. 39.2), although other fingers and/or toes may be involved as well.