Beare-Stevenson Cutis Gyrata Syndrome

A number sign (#) is used with this entry because Beare-Stevenson cutis gyrata syndrome (BSTVS) is caused by heterozygous mutation in the FGFR2 gene (176943) on chromosome 10q26.

Clinical Features

Beare et al. (1969) and Stevenson et al. (1978) described a syndrome which was further delineated by Hall et al. (1992). The syndrome consists of craniofacial anomalies, particularly craniosynostosis, and ear defects, cutis gyrata, acanthosis nigricans, anogenital anomalies, skin tags, and prominent umbilical stump. The skin furrows have a corrugated appearance and are widespread. Cutis gyrata variably affects the scalp, forehead, face, preauricular area, neck, trunk, hands, and feet. Craniosynostosis was present in 4 of 6 known cases, with cloverleaf skull in 3 of these. All 6 cases have been sporadic. Increased paternal age supported the possibility of fresh autosomal dominant mutation as the basis of this disorder. Cohen (1988) reviewed 5 patients with Beare-Stevenson cutis gyrata syndrome reported to that time, 2 of whom also presented with craniofacial dysostosis. Bratanic et al. (1994) described this syndrome in an offspring born to a 39-year-old primipara after in vitro fertilization, the sperm donor being her 43-year-old husband. At birth, the female infant showed a high cranial vault with a shortened anteroposterior diameter. The occipital region was flattened and the overlying skin was markedly corrugated, with deep furrows arranged vertically. There were marked corrugations also on the palms and soles, in the lumbosacral region, on all 4 extremities, and partly also on the labia majora. Skull x-rays showed mild cloverleaf configuration with acrocephaly and bitemporal bossing.

Fonseca et al. (2008) reported a girl with Beare-Stevenson syndrome caused by a de novo heterozygous mutation in the FGFR2 gene (S372C; 176943.0016). She presented at birth with hydrocephalus and breech presentation. She was found to have craniosynostosis, cloverleaf skull, cutis gyrata of the posterior scalp, and redundant skin on the nape of the neck. Other features included hypertelorism, prominent eyes, ptosis, downslanting palpebral fissures, midface hypoplasia, low nasal bridge, anteverted nares, small mouth, hypoplastic nails, and anteriorly placed anus. Unusual features included arterial hypertension and optic disc atrophy. She died at age 4 months, after several hospital admissions and surgery.

Slavotinek et al. (2009) reported a boy with Beare-Stevenson cutis gyrata syndrome. Striking craniofacial features were present at birth, including cloverleaf skull with fused sutures, ocular proptosis with hypoplasia of the supraorbital ridges, hypertelorism, strabismus, deep creases below the eyes, a high nasal bridge, midface hypoplasia, high-arched and narrow palate, and bilateral ear creases. Cutaneous features included cutis gyrata and acanthosis nigricans of the posterior scalp, small skin tags, excess neck skin, and a prominent umbilicus with redundant skin. Hydrocephalus with Arnold-Chiari malformation was present, but neurodevelopment was normal. Unusual features included multiple neonatal teeth, gingival hyperplasia, and atresia of the external ear canals.

Molecular Genetics

In 3 patients with sporadic Beare-Stevenson cutis gyrata syndrome, Przylepa et al. (1996) identified 2 different heterozygous mutations in the FGFR2 gene (176943.0015; 176943.0016). No mutations were identified in 2 additional patients, suggesting genetic heterogeneity.

In a boy with Beare-Stevenson cutis gyrata syndrome, Slavotinek et al. (2009) identified a de novo heterozygous 63-bp deletion in the FGFR2 gene (1506del63; 176943.0040). The authors suggested that the deletion may alter the splicing of isoform IIIc, resulting in illegitimate expression and thus a gain of function of FGFR2b.

Nomenclature

Both Beare et al. (1969) and Stevenson et al. (1978) referred to the cutaneous manifestations as 'cutis gyratum' and Bratanic et al. (1994) followed suit. Judging from widespread usage (see 219300, 102100, and 304200) and the medical dictionaries, 'cutis gyrata' appears to be the correct form.