Limb disorders

Gene: AKT3

Comment when marking as ready: Rated red based on feedback from Genomics England Clinical Team

Created: 16 Oct 2018, 3:03 p.m.

Comment on list classification: Rating as red. Insufficient evidence for AKT3 association with polydactyly.

Created: 2 Oct 2018, 3:52 p.m.

Consulting with the Genomics England clinical team as to the appropriate rating of this gene.

Created: 26 Sep 2018, 4:31 p.m.

AKT3 is associated with Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 in OMIM. Mirzaa et al 2013 (PMID: 23592320) state that in MPPH postaxial polydactyly is reported in almost half of individuals but not in any of the cases below reported with MPPH as a result of AKT3.

Riviere et al. (2012) (PMID: 22729224) report different de novo mutations in AKT3 in 2 unrelated individuals with MPPH but neither had synodactyly or polydactyly. Nakamura et al. (2014) (PMID: 23745724) identified a de novo heterozygous N229S mutation in a 2-month-old boy with macrocephaly, cutis marmorata of the distal extremities, and hyperextensibility of the skin (no polydactyly or syndactyly). The phenotype was compatible with megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP); however, the patient had only a skin capillary malformation. Nakamura et al. (2014) concluded that MPPH and MCAP show significant phenotypic overlap and have a common genetic basis.

Poduri et al. (2012) (PMID: 22500628) and Lee et al. (2012) (PMID: 22729223) report cases of somatic AKT3 duplications or variants in patients with hemimegalencephaly (HME).

Created: 26 Sep 2018, 3:44 p.m.

Phenotypes
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 615937

Publications

• 23592320
• 22729224
• 23745724
• 22500628
• 22729223