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

Hoyeraal-Hreidarsson Syndrome (HHS) is a severe X-linked multi-system disorder caused by mutations in the DKC1 gene.

Diagnostic testing:

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  Neuroimaging reports showing cerebellar hypoplasia/atrophy, small brainstem, thin corpus callosum and cerebral calcifications; and

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  Genetic testing for the DKC1.

Physical findings: Individuals with HHS are at risk for:

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  Microcephaly;

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  Delays in intrauterine growth;

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  Intellectual disability;

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  Spastic paresis (weakness or partial loss of voluntary movement);

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  Ataxia (impaired coordination);

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  Immunodeficiency;

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  Progressive bone marrow failure;

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  Myelodysplastic syndrome or acute leukemia;

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  Solid tumors of the head/neck;

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  Pulmonary fibrosis;

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  Hyperpigmentation (darkened patches or spots on the skin) of upper chest/neck;

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  Nail dystrophy;

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  Oral and premalignant leukoplakia affecting oral and gastrointestinal mucosa;

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  Eye abnormalities;

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  Dental abnormalities;

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  Developmental delay;

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  Cerebellar hypoplasia;

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  Bilateral exudative retinopathy; and

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  Intracranial calcifications.

ICD-9: 284; 287.33

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.

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:

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  Clinical history and examination that describes the diagnostic features of the impairment;

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  Laboratory studies including results of genetic testing; and

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  Neuroimaging results.

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