Blepharocheilodontic syndrome

 Blepharocheilodontic syndrome

Overview

Blepharocheilodontic (BCD) syndrome is a rare, inherited genetic disorder present at birth that primarily affects the eyelids (blepharo--), upper lip (-cheilo--), and teeth (-dontic-). It follows an autosomal dominant inheritance pattern and is typically caused by variants in the CDH1 or CTNND1 genes, which disrupt normal cell-to-cell adhesion pathways.

Symptoms

Eye and Eyelid Features

• Ectropion: The lower eyelids turn outward, exposing the inner surface.

• Euryblepharon: The outer part of the lower eyelid sags away from the eye.

• Lagophthalmia: Inability to close the eyelids completely.

• Distichiasis: An extra row of eyelashes grows out of the inner lining of the upper eyelid, which can scratch and damage the cornea.

• Hypertelorism: Widely spaced eyes, often accompanied by a flat face and a high forehead

Oral and Dental Features

• Cleft Lip and Palate: Bilateral (both sides) cleft lip and an opening in the roof of the mouth (cleft palate) are very common.

• Oligodontia / Hypodontia: Fewer teeth than normal.

• Conical Teeth: Primary (baby) and secondary (permanent) teeth are often smaller than usual and cone-shaped.

Skin, Hair, and Nail Features

• Sparse, Fine Hair: Thin or reduced hair growth.

• Abnormal Nails: Dysplastic or malformed fingernails and toenails.

• Ectodermal Dysplasia: General abnormal development of skin, hair, nails, or teeth.

Other Variable Features

• Thyroid Malfunction: Hypothyroidism caused by an absent or malformed thyroid gland.

• Imperforate Anus: Blockage or absence of the anal opening (rare).

• Limb and Digit Anomalies: Fused fingers or toes (syndactyly) or rare limb-reduction defects.

• Neural Tube Defects: Occasional cases of spina bifida

Causes

• CDH1 Gene (Blepharocheilodontic syndrome 1): Located on chromosome 16q22.1, this gene encodes E-cadherin, a protein crucial for cell-to-cell adhesion in tissues. Heterozygous missense mutations in CDH1 accelerate E-cadherin degradation and disrupt its localization at the cell membrane.

• CTNND1 Gene (Blepharocheilodontic syndrome 2): This gene encodes p120 catenin (p120ctn), a protein that binds to E-cadherin to stabilize it at the cell surface. Heterozygous truncating mutations or loss-of-function variants in CTNND1 impair the E-cadherin–p120ctn interaction

• Cell Adhesion Breakdown: The disruption of the E-cadherin–p120ctn complex weakens normal cell-to-cell adhesion.

• Craniofacial and Ectodermal Impairment: This breakdown interferes with the proper embryonic development of the eyelids, upper lip, palate, and teeth, leading to hallmark features like lower-lid ectropion, cleft lip/palate, and cone-shaped or missing teeth.

• Autosomal Dominant: BCD syndrome is inherited in an autosomal dominant manner. An affected individual needs only one copy of the mutated gene (either CDH1 or CTNND1) inherited from an affected parent, or the mutation can occur as a new (de novo) random genetic change in the individual

Diagnosis

Doctors suspect BCD syndrome by observing a triad of major physical features and associated anomalies:

• Eyelid Malformations: Lower eyelid ectropion (turning outward), euryblepharon (widening/sagging of the lid opening), Lagophthalmia (incomplete eye closure), and upper eyelid distichiasis (extra eyelashes growing from the inner lining of the lid).

• Orofacial Clefting: Bilateral cleft lip and cleft palate.

• Dental Anomalies: Oligodontia (missing teeth) and small, cone-shaped primary and permanent teeth.

• Other Signs: Hypertelorism (widely spaced eyes), flat face, high forehead, sparse hair, abnormal nails, and variable systemic features like congenital hypothyroidism or an imperforate anus.

• Targeted Genes: BCD syndrome is divided into subtypes based on the affected gene in the cell-cell adhesion pathway:

• BCD syndrome 1 (BCDS1): Caused by heterozygous mutations in the CDH1 gene.

• BCD syndrome 2 (BCDS2): Caused by heterozygous mutations in the CTNND1 gene.

• Method: Molecular genetic testing (using blood or saliva samples) confirms the diagnosis by identifying variants in CDH1 or CTNND1 CTNND1

Treatment

• Surgical Reconstruction: Performed by an ophthalmologist or plastic surgeon to correct eyelid malpositions such as lower lid ectropion (turning outward), euryblepharon (enlarged palpebral fissure), ankyloblepharon, and lagophthalmos (incomplete eye closure).

• Procedures: Techniques may include lateral tarsal strips, lateral canthoplasty, tarsorrhaphy, and muscle or cheek advancement.

• Corneal Protection: Lubricating eye drops, ointments, or protective measures are used to prevent corneal abrasions caused by exposure. 

• Cleft Lip Surgery: Typically completed when the child is 3 to 6 months old.

• Cleft Palate Surgery: Usually performed before the child reaches 18 months of age.

• Follow-up Care: Involves oral and maxillofacial surgeons, speech therapy, and early feeding support. 

• Early Evaluations: Dental specialists monitor tooth eruption, which is often delayed in BCD syndrome.

• Restorations: Orthodontic follow-up, implants, or dentures are used to manage oligodontia (missing teeth) and skeletal or jaw alignment. 

• Thyroid Replacement: If congenital hypothyroidism is diagnosed via neonatal screening, daily thyroid hormone replacement therapy is prescribed.

• Orthopedic Support: An orthopedician addresses structural or skeletal issues affecting the spine, legs, hands, or feet.

Type of Doctor Department : Oral and Maxillofacial Surgeon / Dentist ,Ophthalmologist or Oculoplastic Surgeon