U.S. flag

An official website of the United States government

GTR Home > Conditions/Phenotypes > Leukoencephalopathy, ataxia, hypodontia, hypomyelination syndrome

Leukoencephalopathy, ataxia, hypodontia, hypomyelination syndrome

Synonyms
ATAXIA, DELAYED DENTITION, AND HYPOMYELINATION; Hypomyelinating leukodystrophy-ataxia-hypodontia-hypomyelination syndrome; LEUKODYSTROPHY, HYPOMYELINATING, 7, WITH OLIGODONTIA; LEUKODYSTROPHY, HYPOMYELINATING, 7, WITH OLIGODONTIA AND HYPOGONADOTROPIC HYPOGONADISM; LEUKODYSTROPHY, HYPOMYELINATING, 7, WITH OR WITHOUT OLIGODONTIA AND/OR HYPOGONADOTROPIC HYPOGONADISM; LEUKODYSTROPHY, HYPOMYELINATING, 7, WITHOUT OLIGODONTIA OR HYPOGONADOTROPIC HYPOGONADISM; LEUKOENCEPHALOPATHY, HYPOMYELINATING, WITH ATAXIA AND DELAYED DENTITION; Leukodystrophy with oligodontia; Leukodystrophy, hypomyelinating, with hypodontia and hypogonadotropic hypogonadism
Modes of inheritance
Autosomal recessive inheritance (Orphanet)

Summary

Excerpted from the GeneReview: POLR3-Related Leukodystrophy
POLR3-related leukodystrophy, a hypomyelinating leukodystrophy with specific features on brain MRI, is characterized by varying combinations of four major clinical findings: Neurologic dysfunction, typically predominated by motor dysfunction (progressive cerebellar dysfunction, and to a lesser extent extrapyramidal [i.e., dystonia], pyramidal [i.e., spasticity] and cognitive dysfunctions). Abnormal dentition (delayed dentition, hypodontia, oligodontia, and abnormally placed or shaped teeth). Endocrine abnormalities such as short stature (in ~50% of individuals) with or without growth hormone deficiency, and more commonly, hypogonadotropic hypogonadism manifesting as delayed, arrested, or absent puberty. Ocular abnormality in the form of myopia, typically progressing over several years and becoming severe. POLR3-related leukodystrophy and 4H leukodystrophy are the two recognized terms for five previously described overlapping clinical phenotypes (initially described as distinct entities before their molecular basis was known). These include: Hypomyelination, hypodontia, hypogonadotropic hypogonadism (4H syndrome); Ataxia, delayed dentition, and hypomyelination (ADDH); Tremor-ataxia with central hypomyelination (TACH); Leukodystrophy with oligodontia (LO); Hypomyelination with cerebellar atrophy and hypoplasia of the corpus callosum (HCAHC). Age of onset is typically in early childhood but later-onset cases have also been reported. An infant with Wiedemann-Rautenstrauch syndrome (neonatal progeroid syndrome) was recently reported to have pathogenic variants in POLR3A on exome sequencing. Confirmation of this as a very severe form of POLR3-related leukodystrophy awaits replication in other individuals with a clinical diagnosis of Wiedemann-Rautenstrauch syndrome.
Full text of GeneReview (by section):
Summary
Diagnosis
Clinical Characteristics
Genetically Related (Allelic) Disorders
Differential Diagnosis
Management
Genetic Counseling
Resources
Molecular Genetics
Chapter Notes
References
Authors:
Geneviève Bernard
Adeline Vanderver
view full author information

Available tests

25 tests are in the database for this condition.

Check Related conditions for additional relevant tests.

Clinical tests (24 available)

Molecular Genetics Tests

Research tests

Genes See tests for all associated and related genes

  • Also known as: ADDH, C160, HLD7, RPC1, RPC155, WDRTS, hRPC155, POLR3A
    Summary: RNA polymerase III subunit A

  • Also known as: C128, CMT1I, HLD8, INMAP, RPC2, POLR3B
    Summary: RNA polymerase III subunit B

Clinical features

Help
Imported from Human Phenotype Ontology (HPO)

Show allHide all

IMPORTANT NOTE: NIH does not independently verify information submitted to the GTR; it relies on submitters to provide information that is accurate and not misleading. NIH makes no endorsements of tests or laboratories listed in the GTR. GTR is not a substitute for medical advice. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.