Blepharocheilodontic syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Blepharocheilodontic (BCD) syndrome is a disorder that is present at birth. It mainly affects the eyelids (blepharo-), upper lip (-cheilo-), and teeth (-dontic).

People with BCD syndrome have lower eyelids that turn out so that the inner surface is exposed (ectropion). The outside of the lower lid may sag away from the eye (euryblepharon), and the eyelids may not be able to close completely (lagophthalmia). There can be extra eyelashes (distichiasis) on the upper eyelids, ranging from a few extra eyelashes to a full extra set. These eyelashes do not grow along the edge of the eyelid with the normal lashes, but out of its inner lining. When the abnormal eyelashes touch the eyeball, they can cause damage to the clear covering of the eye (cornea). Affected individuals may also have widely spaced eyes (hypertelorism), a flat face, and a high forehead.

Other features of BCD syndrome usually include openings on both sides of the upper lip (bilateral cleft lip) and an opening in the roof of the mouth (cleft palate). Affected individuals may have fewer teeth than normal (oligodontia) and their teeth are often smaller than usual and cone-shaped. The dental abnormalities affect both primary teeth (sometimes called "baby teeth") and secondary (permanent) teeth. Other frequent features include sparse, fine hair and abnormal nails.

Occasionally people with BCD syndrome have additional features, including an obstruction of the anal opening (imperforate anus); malformation or absence of the butterfly-shaped gland in the lower neck called the thyroid, resulting in lack of thyroid gland function; or fused fingers or toes (syndactyly). Very rarely, affected individuals have incompletely formed arms or legs (limb reduction defects) or a spinal cord abnormality known as spina bifida.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

BCD syndrome is caused by mutations in the CDH1 or CTNND1 gene. These genes provide instructions for making proteins called epithelial cadherin (E-cadherin) and p120-catenin, respectively. The E-cadherin protein is found within the membrane that surrounds epithelial cells, which are the cells that line the surfaces and cavities of the body, including the inside of the eyelids and mouth. This protein is involved in the attachment of cells to one another (cell adhesion). The p120-catenin protein helps keep E-cadherin in its proper place in the cell membrane, preventing it from being taken into the cell and broken down prematurely. Interactions between the two proteins are also important for other cell processes that are involved in the development of the head and face (craniofacial development), including the eyelids and teeth.

While the specific effects of the CDH1 gene mutations that cause BCD syndrome are not well understood, researchers suggest that the mutations may result in an E-cadherin protein that is unstable and quickly broken down. CTNND1 gene mutations reduce or eliminate the production or function of p120-catenin, so E-cadherin is broken down prematurely. A shortage of these proteins disrupts normal development, especially craniofacial development, which is thought to underlie the features of BCD syndrome.

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.

In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

BCD syndrome is a rare disorder; its prevalence is unknown. At least 50 affected individuals have been described in the medical literature.

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 eyelid morphology · Very frequent (99-80%)

An abnormality of the eyelids.

Distichiasis · Very frequent (99-80%)

Double rows of eyelashes.

Ectropion of lower eyelids · Very frequent (99-80%)

Abnormality of the eye · Frequent (79-30%)

Any abnormality of the eye, including location, spacing, and intraocular abnormalities.

Abnormality of vision · Frequent (79-30%)

Abnormality of eyesight (visual perception).

Carious teeth · Frequent (79-30%)

Caries is a multifactorial bacterial infection affecting the structure of the tooth. This term has been used to describe the presence of more than expected dental caries.

Conductive hearing impairment · Frequent (79-30%)

An abnormality of vibrational conductance of sound to the inner ear leading to impairment of sensory perception of sound.

Conical tooth · Frequent (79-30%)

An abnormal conical form of the teeth, that is, a tooth whose sides converge or taper together incisally.

Other findings in the same source

From: Orphanet

Additional reported features include Euryblepharon (Frequent (79-30%)); Finger syndactyly (Frequent (79-30%)); Hypertelorism (Frequent (79-30%)); Abnormal hair quantity (Occasional (29-5%)); Anal atresia (Occasional (29-5%)); Epidermoid cyst (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Blepharocheilodontic 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 Blepharocheilodontic 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.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

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.