COMPASSIONATE ALLOWANCE INFORMATION

HOYERAAL-HREIDARSSON SYNDROME

ALTERNATE NAMES

Hoyeraal-Hreidarsson Disease; Cerebellar Hypoplasia with Pancytopenia; Progressive Pancytopenia Immunodeficiency Cerebellar Hypoplasia

DESCRIPTION

Hoyeraal-Hreidarsson Syndrome (HHS) is a severe X-linked multi-system disorder that is associated with microcephaly, delays in intrauterine growth, intellectual disability, spastic paresis, ataxia, and immunodeficiency. Other clinical manifestations include hyperpigmentation; nail dystrophy, oral and premalignant leukoplakia affecting oral and gastrointestinal mucosa. Affected individuals have an unusually small and underdeveloped cerebellum, which is the part of the brain that coordinates movement. People with HHS usually develop early onset bone marrow failure, immunodeficiency and pancytopenia. HHS is caused by mutations in the DKC1 gene.

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM CODING

Diagnostic testing: Neuroimaging reports showing cerebellar hypoplasia/atrophy, small brainstem, thin corpus callosum and cerebral calcifications. Genetic testing for the DKC1 gene confirms the clinical diagnosis.

Physical findings: Individuals with HHS are at risk for progressive bone marrow failure, myelodysplastic syndrome or acute leukemia, solid tumors of the head/neck, pulmonary fibrosis, and abnormal pigmentation changes to the upper chest/neck, eye abnormalities, dental abnormalities, developmental delay, cerebellar hypoplasia, bilateral exudative retinopathy, and intracranial calcifications.

ICD-9: 284 (Constitutional aplastic anemia); 287.33

ONSET AND PROGRESSION

HHS usually presents in early childhood and primarily affects males (X-linked disorder). The prognosis is poor due to the severity of the disease course. Progressive bone marrow failure occurs in over 80% of cases and is the primary cause of early mortality.

TREATMENT

There is no cure for this disorder. Treatment is symptom specific and supportive. Aplastic anemia and immunodeficiency are treated with bone marrow/stem cell transplantation. Supportive treatment for gastrointestinal complications and infections is required.

SUGGESTED PROGRAMMATIC ASSESSMENT*

Suggested MER for evaluation:

• Clinical history and examination that describes the diagnostic features of the impairment.

• Laboratory studies including results of genetic testing.

• Neuroimaging results.

SUGGESTED PROGRAMMATIC ASSESSMENT*

DETERMINATION

LISTING

Meets Listing

7.02

7.06

7.10

7.17

11.17

111.17

Equals Listing

* Adjudicators may, at their discretion, use the Medical Evidence of Record or Listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.