The additional genetic diagnosis of homozygous sickle cell disease in a patient with Waardenburg-Shah syndrome: a case report.

Background: It is important that multiple genetic diagnoses are not missed. This case report describes the clinical features and management of a patient with co-inheritance of Waardenburg syndrome type 4 or Waardenburg-Shah syndrome, an extremely rare disease, and homozygous sickle cell disease not uncommon in the Caribbean. This case is unusual as it may be the first documented case of the co-inheritance of both these diseases. Given the commonality of sickle cell and related hemoglobinopathies, such combined disorders are likely to be under-reported. Importantly, reporting this case will add to the medical literature as it will raise awareness of the phenotypic manifestations of this disorder.

Case Presentation: A 54-year-old Afro-Caribbean woman had a delayed diagnosis of homozygous sickle cell disease at 7 years of age by hemoglobin electrophoresis. The complications of sickle cell disease she experienced included bone pain, a chronic right leg ulcer, avascular necrosis of her left hip, and symptomatic cholelithiasis. This diagnosis was preceded by an earlier diagnosis of Waardenburg syndrome. The basis for the diagnosis of Waardenburg-Shah syndrome was the presence of pigmentary disturbances of her eyes (hypoplastic blue irides), congenital sensorineural hearing loss, and Hirschsprung's disease. She was mute and complained of chronic constipation which required disimpaction on several occasions. She attended a school for the deaf and communicated via writing. A Duhamel procedure bypassing her rectum was performed at age 9. She died following an admission for acute chest syndrome complications.

Conclusion: Sickle cell disease can be diagnosed by newborn screening but, as in this case, may have a delayed presentation. The delay in diagnosis of homozygous sickle cell disease illustrates that other genetic disorders should be considered in patients who already have a diagnosis of one Mendelian disorder but show atypical features.