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overgrowth syndrome - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

overgrowth syndrome

MONDO:0019716

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Overview

A group of syndromes caused by genetic birth defects that may lead to the development of malignancies. It is characterized by a large body size or large body parts at birth, or excessive body growth early in childhood. Representative examples include neurofibromatosis, Beckwith-Wiedemann syndrome, and Sturge-Weber syndrome.

OnsetANTENATAL, INFANTILE, NEONATAL

Clinical Trials7 registered · 2 recruiting

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

No HPO annotations are available for this condition.

Age of onset: before birth, infancy, newborn period.

GeneReviews

Clinical Guidance

PIK3CA-related overgrowth spectrum (PROS) includes overgrowth of a broad range of tissues that may or may not be accompanied by cellular dysplasia. Prior to the understanding of the molecular nature of PROS, a number of distinct but overlapping phenotypes were clinically described and given names . In general, PROS can be divided into an isolated form (when a person has a focal lesion that affects only one tissue or body part; see ) and a syndromic form (i.e., overgrowth plus at least two other features in two systems; see ). A targeted therapy aimed at inhibiting PI3K-related pathway overgrowth has been approved by the FDA . Table 2. Selected Isolated PIK3CA-Related Overgrowth Phenotypes by Affected Organ or Tissue

Diagnosis

Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.

GeneReviews

Diagnostic Criteria

PIK3CA-related overgrowth spectrum (PROS) encompasses a range of clinical findings in which the core features are congenital or early-childhood onset of segmental/focal overgrowth with or without cellular dysplasia in the absence of a family history of similarly affected individuals (i.e., single occurrence in a family). Prior to the identification of PIK3CA as the causative gene, PROS was separated into distinct clinical syndromes based on the tissues and/or organs involved .

Suggestive Findings

PROS should be considered in individuals with the following clinical, brain MRI, and family history findings .

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

No approved treatments are currently available for overgrowth syndrome. The disease remains an area of unmet medical need.

Gene therapy approaches for overgrowth syndrome have been reported in the published literature.

GeneReviews

Management Guidelines

Clinical practice guidelines for PIK3CA-related overgrowth spectrum have been published (full text). Additionally, a targeted pharmacologic therapy has been FDA approved .

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual with PIK3CA-related overgrowth spectrum (PROS), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Note: Assessment is complicated by variable findings in individuals with this condition. Accurate and thorough assessment of medical history is necessary to evaluate for vascular malformations as well as other clinical features.

Prognosis

Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.

GeneReviews

Surveillance Guidelines

Table 8. Recommended Surveillance for Individuals with PIK3CA-Related Overgrowth Spectrum

System/Concern

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

7 clinical trials registered, 2 recruiting. Interventions under study include other interventions and drug therapy. Pipeline includes 1 PHASE4, 1 PHASE1, 2 NA. Research is sponsored by a mix of industry and academic institutions.

NCT ID	Title	Phase	Sponsor	Status
[NCT06721884](https://clinicaltrials.gov/study/NCT06721884)

Data assembled from 5 of 12 sources · Last updated Sep 20, 2026, 11:12 AM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

Orphanet

European rare disease database

Orphanet:93460

GARD

Genetic and Rare Diseases Info Center

GARD:19213

Questions for Your Care Team

→Are any of the 7 active clinical trials a good fit for my situation?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

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Organ or Tissue	Phenotype	Comment
Brain/Head	HMEG: brain overgrowth affecting 1 hemisphere w/or w/o cortical dysplasia	Cognitive developmental disabilities; Seizures are common.; Focal neurologic deficits may be present.; May result in facial asymmetry Focal cortical dysplasia1
Limb	Hemihyperplasia	May incl whole limb, part of limb, or only hand or foot (acral overgrowth); May involve soft tissue, muscle, /or bone Macrodactyly
Lymphatics7	Isolated lymphatic malformations: dilated vascular channels lined by lymphatic endothelial cells	Fluid-filled cysts usually grow proportionally w/growth of affected person; may pain /or morbidity if they are infiltrative.
Vascular7	Vascular malformations	Incl capillary, venous, or mixed malformations Skin

GeneReviews

Differential Diagnosis

A number of overgrowth and megalencephaly disorders overlap with the PIK3CA-related overgrowth spectrum (PROS), including those summarized in . Table 4. Genes of Interest in the Differential Diagnosis of PIK3CA-Related Overgrowth Spectrum (PROS)

Gene(s)	Disorder	MOI	Clinical Features of Disorder
Proteus syndrome	NA (somatic)	Focal somatic overgrowth, epidermal nevi, vascular malformations, dysplastic adipose tissue	Cerebriform 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 somatic	Brain overgrowth (MEG), polymicrogyria, hydrocephalus, polydactyly, connective tissue or joint laxity	Absence 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)
Smith-Kingsmore syndrome	AD (de novo) or somatic	Brain overgrowth (MEG), polymicrogyria, cutaneous findings (incl hyperpigmented nevi)	Absence of consistent vascular/lymphatic malformations PTCH1 SUFU
Basal cell nevus syndrome	AD	Brain overgrowth (MEG), polydactyly, syndactyly	Calcine calcification, BCCs, jaw cysts, epidermal cysts, wide ribs, many other skeletal other multisystem features
PTEN	PTEN hamartoma tumor syndrome (PHTS)	AD	Brain overgrowth (MEG), vascular malformations (incl capillary malformations), lipomas

Source: GeneReviews — "PIK3CA-Related Overgrowth Spectrum"

Research Type	Count	% of Total
Patient case studies	24	36%
Laboratory research	19	29%
Research summaries	9	14%
Disease patterns and progression	5	8%
Clinical study results	4	6%
Testing and diagnosis research	3	5%
New treatment approaches	2	3%

overgrowth syndrome

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Evaluations Following Initial Diagnosis

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

Orphanet

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Clinical Trials

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