Barber-Say Syndrome

Barber-Say syndrome (BSS) is an extremely rare congenital disorder characterized by excessive hair growth (hypertrichosis), delicate (atrophic) skin, eyelid abnormalities (ectropion), and an unusually wide mouth (macrostomia).

Barber-Say syndrome shares phenotypic similarities with Ablepharon macrostomia syndrome, which is also linked to dominant mutations in TWIST2.

Signs and Symptoms

• Pronounced hypertrichosis, particularly on the back

• Skin irregularities, including hyperlaxity and excess

• Facial abnormalities, such as macrostomia

• Eyelid abnormalities

• Unusual and low-positioned ears

• Bulbous nasal tip with underdeveloped alae nasi

• Low frontal hairline

Genetics

Several instances of parent-to-child transmission suggest that Barber-Say syndrome follows an autosomal dominant inheritance pattern. Exome sequencing and expression research have identified that BSS results from mutations in the TWIST2 gene, impacting a highly conserved residue of TWIST2 (twist-related protein 2). TWIST2 is a basic helix-loop-helix transcription factor that binds to E-box DNA motifs (5'-CANNTG-3') as a heterodimer and suppresses transcriptional activation. Since TWIST2 is involved in mesenchymal stem cell differentiation and prevents premature or misplaced osteoblast differentiation, mutations in TWIST2 that impair these functions by altering DNA-binding activity could account for many BSS phenotypes.

Diagnosis

Barber-Say Syndrome is a rare genetic disorder characterized by a range of symptoms. The diagnosis typically involves the following steps:

Clinical Evaluation

Medical History: Gathering information about the patient's symptoms, family history, and any developmental milestones. - Physical Examination: Assessing physical features and any associated anomalies.

Genetic Testing

Next-Generation Sequencing: This can identify mutations in the genes associated with Barber-Say Syndrome, primarily in the KMT2A gene. - Targeted Mutation Analysis: If a specific mutation is known in the family, testing can focus on that mutation.

Imaging Studies

MRI or CT Scans: These may be used to assess any structural abnormalities in the brain or other organs.

Multidisciplinary Approach

Consultations: Involvement of specialists such as geneticists, neurologists, and developmental pediatricians for comprehensive evaluation.

Exclusion of Other Conditions

Differential Diagnosis: Ensuring that symptoms are not attributed to other syndromes or genetic disorders. Early diagnosis is crucial for management and support for individuals with Barber-Say Syndrome.

Treatment

Barber Say syndrome, a rare genetic disorder characterized by various physical and developmental symptoms, requires a multidisciplinary approach for management. The treatment is generally focused on alleviating symptoms and improving the quality of life. Here are some common treatment options:

1. Medical Management

• Regular Monitoring: Regular check-ups with healthcare professionals to monitor growth, development, and any associated health issues.

  
  

• Medications: Depending on symptoms, medications may be prescribed to manage specific issues such as seizures, if present.

  
  

2. Physical Therapy

• Rehabilitation: Physical therapy can help improve motor skills and coordination, addressing any developmental delays.

  
  

3. Occupational Therapy

• Skill Development: Occupational therapy may assist in developing daily living skills and enhancing independence.

  
  

4. Speech Therapy

• Communication Skills: Speech therapy can help improve communication abilities, which may be affected in individuals.

Epidemiology

Barber Say syndrome occurs in fewer than 1 in 1,000,000 individuals. By 2017, only 15 cases had been documented in the literature.