Table 4.

Genes of Interest in the Differential Diagnosis of PIK3CA-Related Overgrowth Spectrum (PROS)

Gene(s)DiffDx DisorderMOIClinical Features of DiffDx Disorder
Overlapping w/PROSDifferentiating from PROS
AKT1 Proteus syndrome NA (somatic)Focal somatic overgrowth, epidermal nevi, vascular malformations, dysplastic adipose tissueCerebriform connective tissue nevi & postnatal onset of overgrowth (vs congenital onset in PROS). Absence of characteristic truncal fatty-vascular mass, spinal paraspinal fast-flow lesions, acral abnormalities of CLOVES syndrome
AKT3
CCND2
PIK3R2 		Megalencephaly-polydactyly-polymicrogyria-hydrocephalus (MPPH) syndrome AD (de novo) or somaticBrain overgrowth (MEG), polymicrogyria, hydrocephalus, polydactyly, connective tissue or joint laxityAbsence of consistent vascular/lymphatic malformations or severe focal somatic overgrowth
HRAS
KRAS
NRAS 		Linear nevus sebaceous syndrome (LNSS) (OMIM 163200)NA (somatic)Cutaneous findings (incl epidermal nevi & vascular malformations)Absence of significant tissue overgrowth or more widespread vascular/lymphatic malformations
MTOR Smith-Kingsmore syndrome (SKS) (OMIM 616638)AD (de novo) or somaticBrain overgrowth (MEG), polymicrogyria, cutaneous findings (incl hyperpigmented nevi)Absence of consistent vascular/lymphatic malformations
PTCH1
SUFU 		Basal cell nevus syndrome ADBrain overgrowth (MEG), polydactyly, syndactylyCalcine calcification, BCCs, jaw cysts, epidermal cysts, wide ribs, many other skeletal & other multisystem features
PTEN PTEN hamartoma tumor syndrome (PHTS)ADBrain overgrowth (MEG), vascular malformations (incl capillary malformations), lipomasIntestinal hamartomas, pigmented macules of the penis, absence of significant focal somatic overgrowth, acral deformities, ↑ cancer risk of specific cancer types
SOLAMEN syndrome (phenotypic subtype of PHTS)See footnote 1.Segmental overgrowth, lipomatosis, arteriovenous malformation, epidermal nevi↑ cancer risk (ovarian cystadenoma, multiple breast tumors, thyroid adenomas), fibrocystic breast disease, gingival papules, multinodular goiter
TSC1
TSC2 		Tuberous sclerosis complex (TSC)ADBrain overgrowth (MEG, HMEG, FCD)Absence of striking focal overgrowth & consistent vascular/lymphatic malformations; presence of white nevi, shagreen patches, ↑ multisystem cancer risk

AD = autosomal dominant; AR = autosomal recessive; CLOVES syndrome = congenital lipomatous overgrowth, vascular malformations, epidermal nevi, scoliosis/skeletal and spinal syndrome; DD = developmental delay; DiffDx = differential diagnosis; FCD = focal cortical dysplasia; HMEG = hemimegalencephaly; MEG = megalencephaly; MOI = mode of inheritance; NA = not applicable; PMG = polymicrogyria; XL = X-linked

1.

SOLAMEN syndrome is the consequence of a germline pathogenic variant in PTEN with a somatic mosaic second PTEN variant that gives the phenotype its segmental attributes.

From: PIK3CA-Related Overgrowth Spectrum

Cover of GeneReviews®
GeneReviews® [Internet].
Adam MP, Feldman J, Mirzaa GM, et al., editors.
Seattle (WA): University of Washington, Seattle; 1993-2024.
Copyright © 1993-2024, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2024 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.