Article CMTC – Feb. 2023

Cutis marmorata telangiectatica congenita: Incidence of extracutaneous manifestations and a proposed clinical definition.

CMTC: Incidence of extracutaneous characteristics and a proposed clinical definition

One of the challenges of CMTC is defining exactly what it is and what other things we should worry about if someone has CMTC.

While many vascular birthmarks are defined by the predominant blood vessel that they derive from, such as lymphatic malformations or venous malformations, CMTC is different.   it is defined most often by the pattern of the blood vessels on the skin which form a network-like pattern often in association with areas of skin atrophy.  This problem of definition has also made it more difficult to find the cause or causes of CMTC.

Increasingly causes of vascular birthmarks have been discovered by taking small pieces of skin or other tissue and using genetic testing of those tissues to find mutations. These are called “somatic” mutations because they are only in the affected tissue and not in the blood of affected individuals.

These studies have resulted some very important discoveries. For example many lymphatic malformations are due to mutations in the tissue in a gene called PIK3CA.  Many venous malformations are due to mutations in a gene called Tek.

CMTC and genetic mutations

Some studies have reported a few cases with gene mutations in CMTC but there are small numbers of cases and inconsistent findings.

For example, Schuart et al (Eur J Med Genet 2022;65 (5) 104472) found somatic mutations in 3 patients with “CMTC” due to GNA11, a gene which has been known to cause port-wine birthmarks.  But review of these 3 patients showed a net-like pattern more often seen in Port-wine birthmarks which is a finer net-like pattern that and coarse pattern of CMTC and without areas of depressed (atrophic) skin.

Davies et al  (J Am Acad Dermatol. 2022;87:162-164) reported on 3 cases where somatic mutations in AKT3 pE17 were found.  One of these had pretty classic skin findings of CMTC, but 2 did not.

One condition causing widespread severe CMTC is Adams-Oliver syndrome (AOS).  This condition is due to germline (not just tissue) mutations in several genes including ARHGAP31, DLL4, NOTCH1, RBPJ, DOCK6, and EOGT.  But most patients with CMTC do not have AOS.  More commonly they have more localized CMTC.

Article about CMTC

An important recent paper, entitled “Cutis marmorata telangiectatica congenita: Incidence of extracutaneous manifestations and a proposed clinical definition” by Downey et al published in Pediatric Dermatology in February 2023 (2023;40:820–828; DOI: 10.1111/pde.15377) looked at a large series (78 patients including 47 previously reported cases and 31 new ones) to try to better define diagnostic criteria and look as the presence of absence of extracutaneous findings.  Seventeen of these cases had generalized CMTC and nearly 80% of these fulfilled criteria for the condition Adams-Oliver syndrome (AOS), an inherited condition known to cause severe generalized CMTC.  In the vast majority of other cases, CMTC was confined to one extremity and extra-cutaneous findings were very uncommon.  Most without AOS had and findings such as atrophy, ulcerations or erosions.  However, most did not have other findings outside of the skin except for a minority with limb asymmetry that actually improved over time.  This paper also includes a nice table (Table 2) which lists other conditions which can mimic CMTC including most often reticulate port-wine birthmark (also called capillary malformation) and selected other conditions.

By Prof. Dr. Ilona J. Frieden, kinderdermatoloog, San Francisco, USA