Hoyeraal-Hreidarsson Syndrome

Clinical Characteristics
Ocular Features: 

Little is known about the ocular signs in this rare disorder.  As many patients have systemic features of dyskeratosis congenita, however, it is possible that some of the ocular findings such as conjunctival and corneal scarring and lid margin distortion might be similar.  Hoyeraal-Hreidarsson syndrome, though, is a more severe disease and many infants may die before the mucocutaneous manifestations appear.  At least one patient has had an exudative retinopathy similar to that seen in Revesz syndrome (268130).  Epiphora and a preretinal hemorrhage have also been reported.

Systemic Features: 

Features of pancytopenia usually appear after 5 months of age while growth retardation and microcephaly are evident soon after birth.  The marrow may show progression to myelodysplasia.  Birth weight is usually low.  Truncal ataxia and axial hypotonia have been reported and MRI imaging reveals cerebellar hypoplasia.  Global developmental delay is a common feature and a few patients have seizures.  Susceptibility to infection has been noted but the basis for an immunodeficiency remains elusive.  Some patients have signs of dyskeratosis congenita such as sparse hair, nail dysplasia, and a reticular pattern of skin pigmentation.


This is an X-linked disorder resulting from mutations in the DKC1 gene (Xq28) active in telomere maintainence.  As expected, the vast majority of affected individuals are male but at least 3 females have been reported. The same gene is also mutated in the X-linked form of dyskeratosis congenita (305000) suggesting that the two are allelic or that both are the same disease.  There are clear clinical differences, however, as severe developmental delay, immunodeficiency, cerebellar hypoplasia, and microcephaly are generally not present in the latter disorder.

There is evidence for telomere length variations in this syndrome and in dyskeratosis congenita.  Homozygous mutations in RTEL1 (regulator of telomere length helicase 1) (20q13.33) have also been found in these conditions.

X-linked recessive, carrier mother
X-linked recessive, father affected
Treatment Options: 

No effective treatment has been reported.

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