Disease Profile

Hoyeraal Hreidarsson syndrome

Prevalence ?
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of Onset






Autosomal dominant ?A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease


Autosomal recessive ?Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype


X-linked dominant ?X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.


X-linked recessive ?Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder


Mitochondrial or multigenic ?Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor ?Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.


Not applicable


Other Names (AKA)

Cerebellar hypoplasia with pancytopenia; Growth retardation prenatal with progressive pancytopenia and cerebellar hypoplasia; Hoyeraal-Hreidarsson syndrome;


Blood Diseases; Congenital and Genetic Diseases; Immune System Diseases;


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.

Clinical description
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.

Diagnostic methods
The disorder diagnosis is based on neuroimaging. Molecular genetic testing is needed to confirm diagnosis.

Differential diagnosis
Differential diagnoses include dyskeratosis congenita, Revesz-Debuse syndrome, Pseudo-TORCH syndrome, Fanconi anemia and Nijmegen breakage syndrome.

Antenatal diagnosis
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.

Genetic counseling
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.


This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
80%-99% of people have these symptoms
Cerebellar hypoplasia
Small cerebellum
Underdeveloped cerebellum

[ more ]

Dermal atrophy
Skin degeneration
Failure to thrive
Faltering weight
Weight faltering

[ more ]

Global developmental delay
Decreased immune function
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific

[ more ]

Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation

[ more ]

Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

Short stature
Decreased body height
Small stature

[ more ]

Low platelet count
30%-79% of people have these symptoms
Abnormality of coagulation
Low number of red blood cells or hemoglobin
Cerebral cortical atrophy
Decrease in size of the outer layer of the brain due to loss of brain cells
Excessive wrinkled skin
Generalized hyperpigmentation
Generalized hypopigmentation of hair
Nail dystrophy
Poor nail formation
Oral leukoplakia
Oral white patch
Premature graying of hair
Early graying
Premature graying
Premature greying
Premature hair graying

[ more ]

Sparse scalp hair
Reduced/lack of hair on scalp
Scalp hair, thinning
Sparse, thin scalp hair
sparse-absent scalp hair

[ more ]

5%-29% of people have these symptoms
Abnormal leukocyte morphology
Bone marrow hypocellularity
Bone marrow failure
Cerebral calcification
Abnormal deposits of calcium in the brain
Decreased reflex response
Decreased reflexes

[ more ]



Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Hoyeraal Hreidarsson syndrome. Click on the link to view a sample search on this topic.