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Warburg Micro syndrome

Saturday 30 October 2010

Definition: Warburg Micro syndrome and Martsolf syndrome are clinically overlapping autosomal recessive conditions characterized by congenital cataracts, microphthalmia, postnatal microcephaly, and developmental delay.

The neurodevelopmental and ophthalmological phenotype is more severe in Warburg Micro syndrome in which cerebral malformations and severe motor and mental retardation are common.

While biallelic loss-of-function mutations in RAB3GAP1 are present in the majority of patients with Warburg Micro syndrome; a hypomorphic homozygous splicing mutation of RAB3GAP2 has been reported in a single family with Martsolf syndrome.

Loss-of-function mutations of RAB3GAP1 as well as functionally severe RAB3GAP2 mutations cause Warburg Micro syndrome while hypomorphic RAB3GAP2 mutations can result in the milder Martsolf phenotype.

Thus, a phenotypic severity gradient may exist in the RAB3GAP-associated disease continuum (the "Warburg-Martsolf syndrome") which is presumably determined by the mutant gene and the nature of the mutation.

References

- A homozygous RAB3GAP2 mutation causes Warburg Micro syndrome. Borck G, Wunram H, Steiert A, Volk AE, K├Ârber F, Roters S, Herkenrath P, Wollnik B, Morris-Rosendahl DJ, Kubisch C. Hum Genet. 2010 Oct 22. PMID: 20967465