Leukodystrophy, Hypomyelinating, 12 (HLD12)

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OMIM®: ⁵⁷ Hypomyelinating leukodystrophy-12 (HLD12) is an autosomal recessive neurologic disorder characterized by severely delayed or even lack of psychomotor development that becomes apparent in the first months of life. Patients are markedly disabled, with acquired microcephaly, lack of speech, and often lack of spontaneous movement due to hypotonia and spasticity. Brain imaging shows delayed myelination (summary by Edvardson et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of HLD, see 312080. In a review of the pathogenesis of disorders with prominent dystonia or opisthotonic posturing as a feature, Monfrini et al. (2021) classified HLD12 as belonging to a group of neurologic disorders termed 'HOPS-associated neurologic disorders (HOPSANDs), which are caused by mutations in genes encoding various components of the autophagic/endolysosomal system, including VPS11. (616683) (Updated 08-Dec-2022)

MalaCards based summary: Leukodystrophy, Hypomyelinating, 12, also known as hypomyelinating leukodystrophy 12, is related to pelizaeus-merzbacher disease and hypomyelinating leukodystrophy. An important gene associated with Leukodystrophy, Hypomyelinating, 12 is VPS11 (VPS11 Core Subunit Of CORVET And HOPS Complexes), and among its related pathways/superpathways are Nanog in Mammalian ESC Pluripotency and Beta-Adrenergic Signaling. Affiliated tissues include brain and peripheral nerve, and related phenotypes are intellectual disability and global developmental delay

Orphanet: ⁵⁸ A rare genetic leukodystrophy identified in families of Ashkenazi Jewish descent, characterized by infancy onset of severe global developmental delay with very limited or absent speech and sometimes complete absence of motor development, hypotonia, spasticity, and acquired microcephaly. Seizures, hearing loss, visual impairment, and autonomic dysfunction have also been described. Brain imaging shows delayed myelination and other white matter abnormalities.

Disease Ontology: ¹¹ A hypomyelinating leukodystrophy characterized by autosomal recessive inheritance of severely delayed or even lack of psychomotor development that becomes apparent in the first months of life, acquired microcephaly and delayed myelination that has material basis in homozygous mutation in the VPS11 gene on chromosome 11q23.

UniProtKB/Swiss-Prot: ⁷³ An autosomal recessive neurologic disorder characterized by developmental delay, spasticity, truncal hypotonia, acquired microcephaly, intellectual disability with variable seizure disorder, accompanied by thin corpus callosum, paucity of white matter and delayed myelination.

Clinical features from OMIM®:

Search Clinical Trials, NIH Clinical Center for Leukodystrophy, Hypomyelinating, 12