Table 3.

Syndromes of Known Genetic Cause in Which CMTC or CMTC-Like Lesions Are Present

Involved Genes /
Chromosomes		SyndromeGenetic Mechanism (MOI)Key Features / Comment
ARHGAP3
DLL4
DOCK6
EOGT
NOTCH1
RBPJ 		Adams-Oliver syndrome (OMIM PS100300)Germline pathogenic variant(s) (AD, AR)Should be suspected in any persons w/CMTC in combination w/aplasia cutis congenita of scalp, terminal transverse limb reduction defects, complex congenital heart disease, or dilated, tortuous vein(s) on scalp
BRD4
HDAC8
NIPBL
RAD21
SMC1A
SMC3 		Cornelia de Lange syndrome Germline pathogenic variant (AD, XL) 1Cutis marmorata that is much more prominent than expected & is persistent (60% of affected persons); also assoc w/synophrys, growth failure, feeding difficulties, limb deformity, ID
CBS
MTHFR 		Homocystinuria (See Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency.)Germline pathogenic variants (AR)Cutis marmorata that is much more prominent than expected & persistent; also assoc w/tall stature, ectopia lentis, DD
RASA1 RASA1-related Parkes Weber syndrome (See Capillary Malformation-Arteriovenous Malformation Syndrome.)Germline pathogenic variant (AD)Capillary malformations (sometimes reticulate or lace-like) ± overgrowth
POLE IMAGE-I syndrome (OMIM 618336) / FILS syndrome (OMIM 615139)Germline pathogenic variants (AR)CMTC-like lesions (often present at birth), IUGR, short stature, metaphyseal dysplasia, immunodeficiency, congenital adrenal hypoplasia
GNA11 Diffuse capillary malformation w/overgrowth 2Postzygotic (mosaic)Capillary malformations (sometimes reticulate or lace-like) ± overgrowth
GNA11 Phakomatosis pigmentovascularis type V (phakomatosis cesiomarmorata)Postzygotic (mosaic)Should be suspected in any person w/CMTC & extensive or unusual & permanent common dermal melanocytosis (previously called "Mongolian spots") or other forms of uncommon dermal melanocytosis. 3 This is important to identify, due to the risk of melanoma in this condition. Multiple café au lait spots, often atypical, may develop over time. Hemihypoplasia & GNA11 mosaic activating variants may also be seen. 4
GNAQ Sturge-Weber syndrome (OMIM 185300)Postzygotic (mosaic)Capillary malformations (sometimes reticulate or lace-like) ± overgrowth; also assoc w/overgrowth of affected tissue
PIK3CA PIK3CA-related overgrowth spectrum Postzygotic (mosaic)Capillary malformations (sometimes reticulate or lace-like) ± overgrowth; also assoc w/overgrowth of affected tissue
Chromosome 13Patau syndromeTrisomyCutis marmorata that is much more prominent than expected & persistent; also assoc w/cardiac, ocular, renal & brain malformations, & polydactyly
Chromosome 18Edward syndromeCutis marmorata that is much more prominent than expected & persistent; also assoc w/IUGR & neural tube & abdominal wall defects.
Chromosome 21Down syndromeCutis marmorata that is much more prominent than expected & persistent; also assoc w/hypotonia, specific facial features, & complex congenital heart disease

AD = autosomal dominant; AR = autosomal recessive; DD = developmental delay; ID = intellectual disability; IUGR = intrauterine growth restriction, MOI = mode of inheritance; XL = X-linked

1.

NIPBL-related Cornelia de Lange syndrome (CdLS), RAD21-related CdLS, SMC3-related CdLS, and BRD4-related CdLS are inherited in an autosomal dominant manner; HDAC8-related CdLS and SMC1A-related CdLS are inherited in an X-linked manner.

2.
3.
4.

From: Isolated and Classic Cutis Marmorata Telangiectatica Congenita

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