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The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
Orpha Number: 3322
An X-linked syndromic intellectual disability considered to be a severe variant of dyskeratosis congenita characterized by intrauterine growth retardation, microcephaly, cerebellar hypoplasia, progressive combined immune deficiency and aplastic anemia.
Hoyeraal-Hreidarsson syndrome (HHS) prevalence is unknown. The syndrome may be underdiagnosed due to high mortality rates.
The disease generally presents in early childhood and primarily affects males. Growth retardation is usually of prenatal onset. Other clinical manifestations include microcephaly, mucocutaneous lesions (hyperpigmentation, nail dystrophy, premalignant leukoplakia affecting oral and gastrointestinal mucosa), early onset bone marrow failure, immunodeficiency and pancytopenia. Cancer predisposition is also reported.
HSS is caused by mutations in the DKC1 gene (Xq28), encoding the nucleolar protein dyskerin which interacts with the human telomerase RNA complex. Mutations in other genes ( TERT , RTEL1 or TINF2 , ACD , PARN ) involved in telomere maintenance may be associated with this disorder.
The disorder diagnosis is based on neuroimaging. Molecular genetic testing is needed to confirm diagnosis.
Differential diagnoses include dyskeratosis congenita, Revesz-Debuse syndrome, Pseudo-TORCH syndrome, Fanconi anemia and Nijmegen breakage syndrome.
Intrauterine growth failure and cerebellar hypoplasia can be detected by prenatal imaging (ultrasounds, MRI). If the familial mutation is known, prenatal genetic testing can be proposed.
HHS follows an X-linked recessive pattern of inheritance. The disorder is very rarely inherited as an autosomal recessive form.
Management and treatment
The aplastic anemia and immunodeficiency can be treated by bone marrow transplantation. Supportive treatment for gastrointestinal complications and infections is required.
The prognosis is poor as the disease follows a very severe course and premature death in childhood can occur due to bone marrow failure, but survival into adulthood is possible.
Visit the Orphanet disease page for more resources.
Source: GARD Last updated on 05-01-20
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