Disorders associated with Hirschprungs disease

Waardenburg Syndrome

Genetic Basis:

• Abnormal distribution of melanocytes due to neural crest abnormalities

• Autosomal dominant inheritance

Clinical Features:

• Broad nasal root

• Lateral displacement of medial canthi with dystopia of lacrimal puncta

• Pigmentary abnormalities of the iris

• Hypertrichosis of the medial part of the eyebrows

• White forelock

• Deaf-mutism (sensorineural hearing loss)

Types:

• Type 1:

  • Mutations in the PAX3 gene

  • Clinical manifestations include congenital sensorineural deafness, dystopia canthorum (lateral displacement of the medial corners of the eyes), neural tube defects, cleft palate and lip, and patchy depigmentation of hair and skin

  • Associated with pigmentary abnormalities of the eyes

• Type 2:

  • Mutations in the MITF gene

  • Normal inner canthi of both eyes but shares other features with Type 1

• Type 3:

  • An extreme presentation of Type 1 with additional abnormalities of the upper limbs

• Type 4 (Shah Waardenburg):

  • Mutations in the EDNRB or endothelin-3 genes

  • Usually autosomal recessive

  • Associated with Hirschsprung’s disease

    
    

References

Ahmed jan N, Mui RK, Masood S. Waardenburg Syndrome. [Updated 2023 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560879/