Table 3. [Selected Syndromic PIK3CA-Related Overgrowth Phenotypes]. - GeneReviews®

Phenotype ¹	Types of Overgrowth	Malformations/Abnormalities
CLOVES (See Figure 1.)	Asymmetric Congenital lipomatous overgrowth of limb or on trunk Hand &/or foot Plantar-palmar overgrowth	Typically lymphatic low flow in areas of overgrowth Linear EN Morbid paraspinal high-flow lesions & phlebectasia	Scoliosis Spina bifida Pectus deformities Sandal-gap toes Splayed feet & toes Macro-, poly-, & syndactyly Chondromalacia patellae Dislocated knees	Renal agenesis/ hypoplasia Splenic lesions Wilms tumor	HMEG Seizures
CLAPO	Partial/generalized of soft tissues & bone	Lower-lip capillary malformation w/o progression Lymphatic malformation of face/neck & upper body
FH or FAO	Segmental & progressive overgrowth of subcutaneous & visceral fibroadipose tissue Occasional skeletal overgrowth Disproportionate linear overgrowth	Vascular malformation EN	Progressive skeletal overgrowth (preserved architecture) Polydactyly Lipomatous infiltration of muscle	Testicular or epididymal cysts & hydrocele Non-spleen/ thymus visceral overgrowth
HHML	Asymmetric overgrowth of a body part or body segment Overgrowth may be static or mildly progressive.	Multiple lipomas
KTS	Bone &/or soft tissue overgrowth in a unilateral limb	Low-flow venous or lymphatic malformations Port-wine nevus (capillary malformations)	Digital enlargement
MCAP or M-CM (See Figures 2, 3.)	Megalencephaly & HMEG ² Generalized overgrowth (macrosomia)	Cutaneous vascular malformations, esp cutis marmorata & capillary malformations of the face	Cutaneous syndactyly & postaxial polydactyly or polysyndactyly Subcutaneous lipomas	Wilms tumor (rare)	Hypotonia Seizures Autistic features Mild-to-severe ID Behavioral problems Meningioma-assoc symptoms (rare)
MPPH ³	Brain overgrowth ⁴		Syndactyly Depressed nasal bridge		DD ID Hypotonia Seizures Medulloblastoma-assoc clinical features (very rare)

Phenotype ¹

Types of Overgrowth

Malformations/Abnormalities

Cutaneous & vascular

Musculoskeletal

Visceral

Neurologic

CLOVES (See Figure 1.)

Asymmetric
Congenital lipomatous overgrowth of limb or on trunk
Hand &/or foot
Plantar-palmar overgrowth

Typically lymphatic low flow in areas of overgrowth
Linear EN
Morbid paraspinal high-flow lesions & phlebectasia

Scoliosis
Spina bifida
Pectus deformities
Sandal-gap toes
Splayed feet & toes
Macro-, poly-, & syndactyly
Chondromalacia patellae
Dislocated knees

Renal agenesis/ hypoplasia
Splenic lesions
Wilms tumor

HMEG
Seizures

CLAPO

Partial/generalized of soft tissues & bone

Lower-lip capillary malformation w/o progression
Lymphatic malformation of face/neck & upper body

FH or FAO

Segmental & progressive overgrowth of subcutaneous & visceral fibroadipose tissue
Occasional skeletal overgrowth
Disproportionate linear overgrowth

Vascular malformation
EN

Progressive skeletal overgrowth (preserved architecture)
Polydactyly
Lipomatous infiltration of muscle

Testicular or epididymal cysts & hydrocele
Non-spleen/ thymus visceral overgrowth

HHML

Asymmetric overgrowth of a body part or body segment
Overgrowth may be static or mildly progressive.

Multiple lipomas

KTS

Bone &/or soft tissue overgrowth in a unilateral limb

Low-flow venous or lymphatic malformations
Port-wine nevus (capillary malformations)

Digital enlargement

MCAP or M-CM (See Figures 2, 3.)

Megalencephaly & HMEG ²
Generalized overgrowth (macrosomia)

Cutaneous vascular malformations, esp cutis marmorata & capillary malformations of the face

Cutaneous syndactyly & postaxial polydactyly or polysyndactyly
Subcutaneous lipomas

Wilms tumor (rare)

Hypotonia
Seizures
Autistic features
Mild-to-severe ID
Behavioral problems
Meningioma-assoc symptoms (rare)

MPPH ³

Brain overgrowth ⁴

Syndactyly
Depressed nasal bridge

DD
ID
Hypotonia
Seizures
Medulloblastoma-assoc clinical features (very rare)

From: PIK3CA-Related Overgrowth Spectrum

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