Townes-Brocks Syndrome

Townes-Brocks Syndrome

Townes-Brocks Syndrome (TBS) is a rare genetic disorder characterized by a triad of imperforate anus, dysplastic ears, and thumb malformations. It is named after Dr. Philip Townes and Dr. Eric Brocks, who first described the condition in 1972.

Key Points:

  • Incidence: Approximately 1 in 250,000 live births
  • Inheritance: Autosomal dominant
  • Gene involved: SALL1 (Spalt-like transcription factor 1)
  • Classic triad: Imperforate anus, dysplastic ears, and thumb malformations

Clinical Features

Townes-Brocks Syndrome presents with a wide spectrum of congenital anomalies, with varying degrees of severity:

  1. Anorectal Malformations:
    • Imperforate anus (most common)
    • Anal stenosis
    • Anteriorly placed anus
  2. Ear Abnormalities:
    • Dysplastic ears (overfolded superior helices, preauricular tags)
    • Sensorineural and/or conductive hearing loss
  3. Hand and Foot Anomalies:
    • Thumb malformations (triphalangeal, bifid, hypoplastic, or preaxial polydactyly)
    • Syndactyly
    • Overlapping toes
  4. Renal Abnormalities:
    • Hypoplastic or dysplastic kidneys
    • Vesicoureteral reflux
    • Renal cysts
  5. Cardiac Defects:
    • Tetralogy of Fallot
    • Ventricular septal defects
    • Patent ductus arteriosus
  6. Other Features:
    • Intellectual disability (in some cases)
    • Growth retardation
    • Genitourinary anomalies (cryptorchidism, hypospadias)
    • Congenital heart defects

Diagnosis

Diagnosis of Townes-Brocks Syndrome is based on clinical findings and genetic testing:

Clinical Diagnosis:

  • Presence of at least two of the following three major features:
    1. Anorectal malformation
    2. Dysplastic ears
    3. Preaxial upper limb malformation
  • Additional supporting features (e.g., renal anomalies, hearing loss)

Genetic Testing:

  • Molecular genetic testing of the SALL1 gene
  • Detection of pathogenic variants in SALL1 confirms the diagnosis

Differential Diagnosis:

Consider other syndromes with overlapping features:

  • VACTERL association
  • Oculo-auriculo-vertebral spectrum
  • Branchio-oto-renal syndrome
  • Cat eye syndrome

Management

Management of Townes-Brocks Syndrome requires a multidisciplinary approach:

Neonatal Period:

  • Evaluation and surgical correction of anorectal malformations
  • Assessment of hearing and cardiac function
  • Renal ultrasound to detect urinary tract anomalies

Ongoing Management:

  • Anorectal Issues: Follow-up for bowel function, potential constipation
  • Hearing: Regular audiological assessments, hearing aids if necessary
  • Renal Function: Monitoring of renal function, management of vesicoureteral reflux
  • Cardiac: Follow-up for any cardiac defects
  • Orthopedic: Management of limb anomalies, potential surgical interventions
  • Developmental: Early intervention programs, special education if needed

Long-term Considerations:

  • Genetic counseling for family planning
  • Psychosocial support for patients and families
  • Regular follow-up with a multidisciplinary team

Genetics

Townes-Brocks Syndrome is caused by mutations in the SALL1 gene:

Inheritance Pattern:

  • Autosomal dominant
  • 50% chance of transmission from an affected parent to offspring
  • About 50% of cases result from de novo mutations

SALL1 Gene:

  • Located on chromosome 16q12.1
  • Encodes a zinc finger transcription factor
  • Plays a crucial role in embryonic development

Genotype-Phenotype Correlations:

  • Most pathogenic variants are nonsense or frameshift mutations
  • Missense mutations are rare and may result in milder phenotypes
  • No clear correlation between specific mutations and severity of symptoms

Genetic Testing:

  • Sequence analysis of SALL1
  • Deletion/duplication analysis if sequencing is negative
  • Prenatal testing is possible if the familial mutation is known


Further Reading
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