Details of Disease | DrugMAP

General Information of Disease (ID: DISWECW7)

Disease Name	Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes
Synonyms	overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes
Definition	A disease caused by mosaic gain-of-function (GoF) of several genes in the MTOR pathway (MTOR, PIK3CA, PIK3R2 and AKT3) are functionally the same despite significant phenotypic variability. These GoF variants result in overgrowth due to an over-activation of key genes in this pathway. The phenotypic variability is generally attributed to the mosaic fraction and affected tissue types. For example, macrocephaly is noted if the variant is identified in the brain, but non symmetric overgrowth of that limb is noted when the variant is only present in the affected limb. The pathologies of the affected tissue often reveal similar characteristics such as cellular overgrowth. However, this is not always the case especially with focal cortical dysplasia. At times the characteristics pathologies are not present in the tissue but sampling biases are an issue. FCD resections often involve a very small area and so a very small amount of tissue is available for pathology and it is not guaranteed that lesional tissue is sent. Therefore, having a single disease term which can encompass the phenotypic variability yet provide a unifying molecular diagnosis name makes sense given the common functional mechanism.
Disease Hierarchy	DISOV08L: Central nervous system malformation DISWECW7: Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 3 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
AKT3	TTAZ05C	Definitive	Autosomal dominant	[1]
MTOR	TTCJG29	Definitive	Autosomal dominant	[1]
PIK3CA	TTEUNMR	Definitive	Autosomal dominant	[1]
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This Disease Is Related to 4 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
AKT3	OT5M2LFI	Definitive	Autosomal dominant	[1]
MTOR	OTHH8KU7	Definitive	Autosomal dominant	[1]
PIK3CA	OTTOMI8J	Definitive	Autosomal dominant	[1]
PIK3R2	OTZSUQK5	Definitive	Autosomal dominant	[1]
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References

1	Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.