Intellectual disability syndromic and non-syndromic
Gene: D2HGDH

D2HGDH (D-2-hydroxyglutarate dehydrogenase)
EnsemblGeneIds (GRCh38): ENSG00000180902
EnsemblGeneIds (GRCh37): ENSG00000180902
OMIM: 609186, Gene2Phenotype
D2HGDH is in 13 panels

1 review

Sumudu Perera (Royal Melbourne Hospital)

Green List (high evidence)

Phenotype:
Struys et al. (2005) (PMID: 15609246) describes two patients. Patient 1 with mild facial dysmorphia, with a reduced bitemporal diameter, a prominent forehead, micrognathia and psychomotor retardation in addition to tonic, tonic-clonic, and myoclonic seizures that were not responsive to antiepileptic treatment. Was homozygous for a missense mutation. Functional studies for patient 1: Overexpression studies in HEK293 cells of the mutant missense protein showed a marked reduction of D-2-hydroxyglutarate dehydrogenase activity.

Patient 2 with generalized tonic-clonic seizures, infantile spasms with hypsarrhythmia, hypotonia, a movement disorder, cortical blindness, and developmental delay. Was compound heterozygous for a missense mutation.

Misra et al. (2005) (PMID: 16081310) assessed two monozygotic twin sisters, with compound heterozygosity for 2 mutations in the D2HGDH gene, with vastly different phenotypes. One had multiple congenital anomalies, hypotonia, severe developmental delay, epileptic encephalopathy, and cortical atrophy with periventricular leukomalacia. In contrast, her sister had a normal neurocognitive and neuroradiologic phenotype without congenital abnormalities. Both had distinctive facial features: dolichocephaly, malar flattening, and broad nasal root.

Biase et al. (2024) (PMID: 38825343) reported an infant with speech delay, developmental delay, and autism spectrum; Mild developmental delays were noted around 10 months. Speech delay, attention deficit hyperactivity disorder, and behavior issues were identified at 5 years. Found to have in-trans compound heterozygous D2HGDH variants.

Functional assays: PMID: 31349060, 20020533
Created: 29 Aug 2024, 2:18 a.m. | Last Modified: 29 Aug 2024, 2:18 a.m.

Panel Version: 0.6123

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
D-2-hydroxyglutaric aciduria MIM#600721

Publications

Variants in this GENE are reported as part of current diagnostic practice

Created: 29 Aug 2024, 2:18 a.m.
Last Modified: 29 Aug 2024, 2:18 a.m.
Panel version: 0.6123

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Green
Genetic Health Queensland

Phenotypes

D-2-hydroxyglutaric aciduria MIM#600721

OMIM

609186

Clinvar variants

Variants in D2HGDH

Penetrance

None

Publications

Panels with this gene