Beare-Stevenson cutis gyrata syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Beare-Stevenson cutis gyrata syndrome is a genetic disorder that typically features skin abnormalities and the premature fusion of certain bones of the skull (craniosynostosis). This early fusion prevents the skull from growing normally and affects the shape of the head and face.

Many of the characteristic facial features of Beare-Stevenson cutis gyrata syndrome result from the premature fusion of the skull bones. The head is unable to grow normally, which leads to a cloverleaf-shaped skull, wide-set and bulging eyes, ear abnormalities, and an underdeveloped upper jaw. Early fusion of the skull bones also affects the growth of the brain, causing delayed development and intellectual disability.

A skin abnormality called cutis gyrata is also characteristic of this disorder. The skin has a furrowed and wrinkled appearance, particularly on the face, near the ears, and on the palms and soles of the feet. Additionally, thick, dark, velvety areas of skin (acanthosis nigricans) are sometimes found on the hands and feet and in the genital region.

Additional signs and symptoms of Beare-Stevenson cutis gyrata syndrome can include a blockage of the nasal passages (choanal atresia), a malformation of the airways (tracheal cartilaginous sleeve), overgrowth of the umbilical stump (tissue that normally falls off shortly after birth, leaving the belly button), and abnormalities of the genitalia and anus. The medical complications associated with this condition are often life-threatening in infancy or early childhood.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Mutations in the FGFR2 gene cause Beare-Stevenson cutis gyrata syndrome. This gene produces a protein called fibroblast growth factor receptor 2, which plays an important role in signaling a cell to respond to its environment, perhaps by dividing or maturing. A mutation in the FGFR2 gene alters the protein and promotes prolonged signaling, which is thought to interfere with skeletal and skin development.

Some individuals with Beare-Stevenson cutis gyrata syndrome do not have identified mutations in the FGFR2 gene. In these cases, the cause of the condition is unknown.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. All reported cases have resulted from new mutations in the gene, and occurred in people with no history of the disorder in their family.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Beare-Stevenson cutis gyrata syndrome is a rare genetic disorder; its incidence is unknown. Approximately 25 people with this condition have been reported worldwide.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal skull morphology · Very frequent (99-80%)

An abnormality of the skull, the bony framework of the head which is comprised of the neurocranium (with eight cranial bones) and the viscerocranium (facial skeleton) that comprises fourteen facial bones with the mandible as its largest bone.

Abnormality of the face · Very frequent (99-80%)

An abnormality of the face.

Abnormality of the pancreas · Very frequent (99-80%)

An abnormality of the pancreas.

Acanthosis nigricans · Very frequent (99-80%)

A dermatosis characterized by thickened, hyperpigmented plaques, typically on the intertriginous surfaces and neck.

Aplasia/Hypoplasia of the earlobes · Very frequent (99-80%)

Absence or underdevelopment of the ear lobes.

Choanal atresia · Very frequent (99-80%)

Absence or abnormal closure of the choana (the posterior nasal aperture). Most embryologists believe that posterior choanal atresia results from a failure of rupture between the 35th and 38th day of fetal life of the partition which separates the bucconasal or buccopharyngeal membranes. The resultant choanal atresia may be unilateral or bilateral, bony or membranous, complete or incomplete. In over 90 per cent of cases the obstruction is bony, while in the remainder it is membranous. The bony type of atresia is commonly located 1-2 mm. anterior to the posterior edge of the hard palate, and the osseous septum varies in thickness from 1 to 10 mm. In the membranous form of choanal atresia the obstruction usually occurs further posteriorly. In approximately one third of cases the atresia is bilateral.

Cloverleaf skull · Very frequent (99-80%)

Trilobar skull configuration when viewed from the front or behind.

Depressed nasal bridge · Very frequent (99-80%)

Posterior positioning of the nasal root in relation to the overall facial profile for age.

Dolichocephaly · Very frequent (99-80%)

An abnormality of skull shape characterized by a increased anterior-posterior diameter, i.e., an increased antero-posterior dimension of the skull. Cephalic index less than 76%. Alternatively, an apparently increased antero-posterior length of the head compared to width. Often due to premature closure of the sagittal suture.

Downslanted palpebral fissures · Very frequent (99-80%)

The palpebral fissure inclination is more than two standard deviations below the mean.

Hearing abnormality · Very frequent (99-80%)

An abnormality of the sensory perception of sound.

Hypoplasia of the zygomatic bone · Very frequent (99-80%)

Underdevelopment of the zygomatic bone. That is, a reduction in size of the zygomatic bone, including the zygomatic process of the temporal bone of the skull, which forms part of the zygomatic arch.

Macrotia · Very frequent (99-80%)

Median longitudinal ear length greater than two standard deviations above the mean and median ear width greater than two standard deviations above the mean (objective); or, apparent increase in length and width of the pinna (subjective).

Malar flattening · Very frequent (99-80%)

Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.

Other findings in the same source

From: Orphanet

Additional reported features include Melanocytic nevus (Very frequent (99-80%)); Midface retrusion (Very frequent (99-80%)); Palmoplantar cutis gyrata (Very frequent (99-80%)); Palmoplantar keratoderma (Very frequent (99-80%)); Preauricular skin furrow (Very frequent (99-80%)); Proptosis (Very frequent (99-80%)); Ptosis (Very frequent (99-80%)); Respiratory distress (Very frequent (99-80%)); Subcutaneous nodule (Very frequent (99-80%)); Tooth agenesis (Very frequent (99-80%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Beare-Stevenson cutis gyrata syndrome is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Beare-Stevenson cutis gyrata syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.