Microcephaly

Gene: DNM1L

Comment when marking as ready: Borderline Amber/Green, but overall a small proportion of individuals have microcephaly.

Created: 2 Sep 2020, 6:33 a.m. | Last Modified: 2 Sep 2020, 6:33 a.m.

Panel Version: 0.306

I don't know

Most individuals reported with variants in DNM1L do not have microcephaly listed as a phenotype.

PMID: 17460227 - Reports a newborn girl with microcephaly (head circumference below the 0.4 percentile), abnormal brain development, optic atrophy and hypoplasia, persistent lactic acidemia, and a mildly elevated plasma concentration of very-long-chain fatty acids. She died suddenly at the age of 37 days. A monoallelic missense variant was identified.

PMID: 26992161 - A monoallelic missense variant reported in a 2 year old boy with a chronic neurological disorder, characterized by postnatal microcephaly (OFC 45.5 cm (<3rd centile)), developmental delay, and pain insensitivity.

PMID: 30801875 - Five patients presenting with severe epileptic encephalopathy; microcephaly (<3rd percentile) reported in one patient. Five de novo dominant DNM1L variants were identified.

Both loss-of-function (variants within the GTPase domain) and dominant negative (variants within the middle domain) mechanisms have been reported.

Created: 2 Sep 2020, 4:58 a.m. | Last Modified: 2 Sep 2020, 4:59 a.m.

Panel Version: 0.273

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1, MIM#614388

Publications

• PMID: 17460227
• 26992161
• 30801875

Mode of pathogenicity
Other