Beare–Stevenson cutis gyrata syndrome

Overview

Beare–Stevenson cutis gyrata syndrome is a very rare genetic disorder characterized by distinctive skin and skull abnormalities, along with various craniofacial and developmental malformations. The name “cutis gyrata” refers to the deeply grooved or ridged appearance of the scalp and skin, resembling brain gyri. First described by Beare and Stevenson in 1993, the syndrome is part of the craniosynostosis syndromes, where premature fusion of skull bones leads to abnormal head shape and facial structure. It is often life-threatening, with most affected infants having severe complications.

Causes

Beare–Stevenson syndrome is caused by a mutation in the FGFR2 gene(fibroblast growth factor receptor 2), which plays a crucial role in bone growth, skin development, and cellular signaling.

• Mutations typically occur spontaneously (de novo) and are not inherited from parents.

• The condition follows an autosomal dominant pattern, but familial transmission is extremely rare due to the high mortality rate in infancy.

• Mutations in FGFR2 affect cell differentiation in bone and skin, leading to premature skull fusion and abnormal skin development.

Symptoms

The hallmark features of Beare–Stevenson syndrome usually present at birth or shortly thereafter:

• Cutis gyrata – deep ridges and folds of the skin, particularly on the scalp, forehead, and face

• Craniosynostosis – early fusion of skull bones, leading to a tower-shaped or asymmetric skull

• Facial abnormalities – including wide-set eyes (hypertelorism), midface hypoplasia, low-set ears, and cleft palate

• Skin tags – especially around the ears and genitalia

• Acrochordons – small fleshy skin growths

• Genital anomalies – such as hypospadias or undescended testes

• Airway obstruction or respiratory distress – due to craniofacial anomalies

Diagnosis

Diagnosis is based on physical features, imaging studies, and genetic testing:

• Clinical examination – revealing characteristic skin and craniofacial features

• CT or MRI of the skull – to confirm craniosynostosis and assess brain structures

• Genetic testing – to identify FGFR2 mutations, which confirms the diagnosis

• Prenatal ultrasound – may detect cranial or facial abnormalities in some cases

Treatment

There is no cure for Beare–Stevenson syndrome, and treatment focuses on managing symptoms and complications:

• Cranial surgery – to relieve pressure caused by craniosynostosis and allow for brain growth

• Airway management – possibly including tracheostomy in severe cases of obstruction

• Plastic or reconstructive surgery – for skin folds, facial anomalies, and cleft palate

• Multidisciplinary care – involving neurosurgeons, dermatologists, ENT specialists, geneticists, and pediatricians

• Supportive care – including nutritional support and physical therapy if needed

Prognosis

The prognosis for Beare–Stevenson syndrome is generally poor:

• Many infants do not survive beyond early childhood due to respiratory complications or brain development issues.

• In rare cases with milder mutations, survival into childhood is possible with intensive medical and surgical care.

• Early intervention can improve quality of life but does not usually alter the severe course of the disorder.