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CLAPO syndrome

MedGen UID:
416522
Concept ID:
C2751313
Congenital Abnormality; Disease or Syndrome
Synonyms: Capillary malformation of the lower lip, lymphatic malformation of face and neck, asymmetry of face and limbs, and partial/generalized overgrowth; LOPEZ-GUTIERREZ SYNDROME
SNOMED CT: Capillary malformation of lower lip, lymphatic malformation of face and neck, asymmetry of face and limbs and overgrowth syndrome (717765001); CLAPO syndrome (717765001); CLAPO (capillary malformation of lower lip, lymphatic malformation of face and neck, asymmetry of face and limbs and overgrowth) syndrome (717765001)
Modes of inheritance:
Unknown inheritance
MedGen UID:
989040
Concept ID:
CN307042
Finding
Source: Orphanet
Hereditary clinical entity whose mode of inheritance is unknown.
 
Gene (location): PIK3CA (3q26.32)
 
Monarch Initiative: MONDO:0013125
OMIM®: 613089
Orphanet: ORPHA168984

Disease characteristics

Excerpted from the GeneReview: PIK3CA-Related Overgrowth Spectrum
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. 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 (e.g., MCAP [megalencephaly-capillary malformation] syndrome and CLOVES [congenital lipomatous asymmetric overgrowth of the trunk, lymphatic, capillary, venous, and combined-type vascular malformations, epidermal nevi, skeletal and spinal anomalies] syndrome). The predominant areas of overgrowth include the brain, limbs (including fingers and toes), trunk (including abdomen and chest), and face, all usually in an asymmetric distribution. Generalized brain overgrowth may be accompanied by secondary overgrowth of specific brain structures resulting in ventriculomegaly, a markedly thick corpus callosum, and cerebellar tonsillar ectopia with crowding of the posterior fossa. Vascular malformations may include capillary, venous, and less frequently, arterial or mixed (capillary-lymphatic-venous or arteriovenous) malformations. Lymphatic malformations may be in various locations (internal and/or external) and can cause various clinical issues, including swelling, pain, and occasionally localized bleeding secondary to trauma. Lipomatous overgrowth may occur ipsilateral or contralateral to a vascular malformation, if present. The degree of intellectual disability appears to be mostly related to the presence and severity of seizures, cortical dysplasia (e.g., polymicrogyria), and hydrocephalus. Many children have feeding difficulties that are often multifactorial in nature. Endocrine issues affect a small number of individuals and most commonly include hypoglycemia (largely hypoinsulinemic hypoketotic hypoglycemia), hypothyroidism, and growth hormone deficiency. [from GeneReviews]
Authors:
Ghayda Mirzaa  |  John M Graham  |  Kim Keppler-Noreuil   view full author information

Clinical features

From HPO
Congenital macrodactylia
MedGen UID:
78564
Concept ID:
C0265552
Congenital Abnormality
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. 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 (e.g., MCAP [megalencephaly-capillary malformation] syndrome and CLOVES [congenital lipomatous asymmetric overgrowth of the trunk, lymphatic, capillary, venous, and combined-type vascular malformations, epidermal nevi, skeletal and spinal anomalies] syndrome). The predominant areas of overgrowth include the brain, limbs (including fingers and toes), trunk (including abdomen and chest), and face, all usually in an asymmetric distribution. Generalized brain overgrowth may be accompanied by secondary overgrowth of specific brain structures resulting in ventriculomegaly, a markedly thick corpus callosum, and cerebellar tonsillar ectopia with crowding of the posterior fossa. Vascular malformations may include capillary, venous, and less frequently, arterial or mixed (capillary-lymphatic-venous or arteriovenous) malformations. Lymphatic malformations may be in various locations (internal and/or external) and can cause various clinical issues, including swelling, pain, and occasionally localized bleeding secondary to trauma. Lipomatous overgrowth may occur ipsilateral or contralateral to a vascular malformation, if present. The degree of intellectual disability appears to be mostly related to the presence and severity of seizures, cortical dysplasia (e.g., polymicrogyria), and hydrocephalus. Many children have feeding difficulties that are often multifactorial in nature. Endocrine issues affect a small number of individuals and most commonly include hypoglycemia (largely hypoinsulinemic hypoketotic hypoglycemia), hypothyroidism, and growth hormone deficiency.
Varicose disease
MedGen UID:
21827
Concept ID:
C0042345
Disease or Syndrome
Enlarged and tortuous veins.
Venous malformation
MedGen UID:
754284
Concept ID:
C2937220
Congenital Abnormality
A vascular malformation resulting from a developmental error of venous tissue composed of dysmorphic channels lined by flattened endothelium and exhibiting slow turnover. A venous malformation may present as a blue patch on the skin ranging to a soft blue mass. Venous malformations are easily compressible and usually swell in thewhen venous pressure increases (e.g., when held in a dependent position or when a child cries). They may be relatively localized or quite extensive within an anatomic region.
Hemihypertrophy
MedGen UID:
90701
Concept ID:
C0332890
Congenital Abnormality
Overgrowth of only one side of the body.
Lymphedema
MedGen UID:
6155
Concept ID:
C0024236
Disease or Syndrome
Localized fluid retention and tissue swelling caused by a compromised lymphatic system.
Capillary malformation of the lip
MedGen UID:
1611689
Concept ID:
C4531089
Anatomical Abnormality
A vascular malformation located in the lip that is characterized by ectatic papillary dermal capillaries and postcapillary venules in the upper reticular dermis.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for CLAPO syndrome in Orphanet.

Recent clinical studies

Etiology

de Kock L, Cuillerier A, Gillespie M, Couse M, Hartley T, Mears W, Bernier FP, Chudley AE, Frosk P, Nikkel SM, Innes AM, Lauzon J, Thomas M, Guerin A, Armour CM, Weksberg R, Scott JN, Watkins D, Harvey S, Cytrynbaum C; Care4Rare Canada Consortium, Kernohan KD, Boycott KM
Am J Med Genet A 2024 Mar;194(3):e63466. Epub 2023 Nov 10 doi: 10.1002/ajmg.a.63466. PMID: 37949664
Rodriguez-Laguna L, Ibañez K, Gordo G, Garcia-Minaur S, Santos-Simarro F, Agra N, Vallespín E, Fernández-Montaño VE, Martín-Arenas R, Del Pozo Á, González-Pecellín H, Mena R, Rueda-Arenas I, Gomez MV, Villaverde C, Bustamante A, Ayuso C, Ruiz-Perez VL, Nevado J, Lapunzina P, Lopez-Gutierrez JC, Martinez-Glez V
Genet Med 2018 Aug;20(8):882-889. Epub 2018 Feb 15 doi: 10.1038/gim.2017.200. PMID: 29446767

Diagnosis

de Kock L, Cuillerier A, Gillespie M, Couse M, Hartley T, Mears W, Bernier FP, Chudley AE, Frosk P, Nikkel SM, Innes AM, Lauzon J, Thomas M, Guerin A, Armour CM, Weksberg R, Scott JN, Watkins D, Harvey S, Cytrynbaum C; Care4Rare Canada Consortium, Kernohan KD, Boycott KM
Am J Med Genet A 2024 Mar;194(3):e63466. Epub 2023 Nov 10 doi: 10.1002/ajmg.a.63466. PMID: 37949664
González-Hermosa MR, Guerra E, Tuduri I, Vicente I, López-Almaraz R
Dermatol Ther 2019 Jul;32(4):e12991. Epub 2019 Jun 20 doi: 10.1111/dth.12991. PMID: 31172613
Downey C, López-Gutiérrez JC, Roé-Crespo E, Puig L, Baselga E
Pediatr Dermatol 2018 Jul;35(4):e243-e244. Epub 2018 May 15 doi: 10.1111/pde.13514. PMID: 29766551
Flores-Terry MÁ, Zamberk-Majlis P, Cortina-de la Calle MP, García-Arpa M
Actas Dermosifiliogr (Engl Ed) 2018 Mar;109(2):180. Epub 2017 May 15 doi: 10.1016/j.ad.2016.10.023. PMID: 28521853

Therapy

Cerejeira D, Vergara-de-la-Campa L, Boixeda P, López-Gutiérrez JC
Actas Dermosifiliogr 2022 May;113(5):505-509. Epub 2021 Oct 5 doi: 10.1016/j.ad.2021.02.020. PMID: 35292145
González-Hermosa MR, Guerra E, Tuduri I, Vicente I, López-Almaraz R
Dermatol Ther 2019 Jul;32(4):e12991. Epub 2019 Jun 20 doi: 10.1111/dth.12991. PMID: 31172613

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