Cutis marmorata telangiectatica congenita: a literature review

Cutis marmorata telangiectatica congenita (CMTC) is a rare congenital vascular anomaly, classified as a simple vascular malformation and subclassified as a capillary malformation (CM) by the International Society for the Study of Vascular Anomalies (ISSVA) [1]. CMTC is described as a persistent reticulated marbled erythema, which blanches with pressure and does not resolve with heating [2, 3]. As it affects capillaries and venules, CMTC is characterised as a slow-flow vascular lesion [4‐6]. The affected cutaneous areas may develop cutaneous atrophy and ulcerations, and may also be associated with body asymmetry. The condition has often been reported as benign; however, associated anomalies such as congenital glaucoma, limb asymmetry and central nervous system involvement are frequently observed, which require the attention of medical professionals [7‐10]. CMTC was first described by the Dutch paediatrician Cato van Lohuizen, who named the condition CMTC [11]. Since then, it has been referred to in the literature under several different terms including congenital generalised phlebectasia [12], naevus vascularis reticularis [13], congenital phlebectasia [14], congenital livedo reticularis [15] and van Lohuizen syndrome [16]. CMTC patients with co-existing Mongolian spots (“blue spots” or dermal melanocytosis) have been described as having phacomatosis pigmentovascularis type V (PPV type V) or phacomatosis cesiomarmorata [17‐19].

Although the aetiology of CMTC remains unknown, two genetic theories were suggested by Rudolf Happle in 2002, who described the concept of an autosomal lethal mutation surviving by mosaicism and the theory of paradominant inheritance [20]. More recent studies identified GNA11 mutations in skin biopsies from CMTC-affected skin areas [21‐23]. In two of these studies, the mutation was either not detectable in blood [23] or found at a low level of 0.3% in blood [22]. CMTC is, however, still a clinical diagnosis [7‐10]. Kienast et al. proposed a set of diagnostic criteria, where the presence of three major and two minor criteria out of five was considered indicative of CMTC [3]. The major criteria include: congenital reticulate (marmorated) erythema, absence of venectasia within the affected region at 1 year orof age, and unresponsiveness to local warming. Minor criteria are: fading of erythema within 2 years, telangiectasia within the CMTC-affected area, port-wine stain outside the CMTC-affected areas, ulceration, and cutaneous atrophy. However, these diagnostic criteria have not been validated. Histopathology does not play a role in the diagnosis of CMTC due to unspecific and inconsistent findings in skin biopsies [7, 24‐26].

In this literature review, we evaluate the proposed criteria of Kienast et al. [3] and address the clinical manifestations, associated anomalies, differential diagnosis, management and prognosis of CMTC.

A literature search was performed in PubMed using the following keywords: cutis marmorata telangiectatica congenita, Van Lohuizen’s syndrome, CMTC, congenital phlebectasia, naevus vascularis reticularis, congenital livedo reticularis, and phacomatosis cesiomarmorata. The MeSH search function in PubMed was also applied. The search retrieved 731 unfiltered articles. All abstracts for the unfiltered articles were reviewed in terms of their relevance to the subject, including synonyms for CMTC. We included articles written in English, German, French, Norwegian, Swedish, Danish and Turkish (Fig. 1).

A total of 193 articles were identified for full-text review. In addition, we searched the reference lists of the identified articles for additional sources, leading to a total of 204 articles for full-text review. A total of 168 articles were deemed relevant for the subject, including 148 original studies. Before exclusion of any articles, they were discussed among all authors.

In those articles with multiple cases consisting of both true CMTC patients and other capillary malformations such as macrocephaly-capillary malformation (M-CMTC, M-CM or M-CAP), Sturge Weber syndrome etc. only the true CMTC cases were included in the count. All uncertain cases were discussed in the study group, so only true CMTC cases were included in our study.

For each original article, the following variables were registered: gender, ethnicity, presence of the proposed diagnostic criteria of Kienast et al., distribution of skin lesions, associated anomalies, histopathology, family history, treatment, and prognosis.

We applied the proposed diagnostic criteria of Kienast et al. [3] to assess CMTC. One of the major criteria is the absence of venectasia; however, we found that phlebectasia was present in 20.4% of the published CMTC patients, suggesting that this major criteria should be reconsidered. Evaluating the diagnostic criteria of Kienast et al. in terms of validity is a challenge due to both the retrospective nature of this review and the amount of missing information for the published patients, ranging from 66.0–88.2%.

Improvement in the marbled skin appearance over time was described in 143 (29.5%) patients (Table 1), whereas 4.5% did not show improvement, and this information was lacking in the remaining 66.0% of patients. There was a wide age span for when improvement was seen. The literature reported that patients between the ages of 6 weeks to 26 years showed improvement of the skin condition [2, 33]; however, many articles did not specify the exact age at improvement. In several articles, improvement was described after 2 years of age [7, 34‐37]. Patients with no improvement of CMTC were also described [15, 17, 38‐43], but some of these patients had a short follow-up [44‐46]. Adults with persistent erythema were also reported [27, 47, 48]. Another issue in the literature was the short follow-up or no follow-up, which makes it challenging to describe the precise prognosis of CMTC.

In the literature, asymmetry was found to be the most frequent anomaly, comprising 37.7%, while the minor criteria “improvement of erythema” should be further investigated as a part of CMTC in future prospective studies.

CMTC is a relatively benign disorder on its own, which does not usually require treatment. However, health care professionals should be aware of the frequently associated anomalies, such as glaucoma and leg length discrepancy, which may have serious consequences if not recognised and treated. We suggest that children with CMTC should be referred to an ophthalmologist after birth for regular check-ups for glaucoma, and that children with CMCT on the legs should be regularly monitored for leg length discrepancy during childhood until the end of the growth period (Fig. 4). Furthermore, we suggest reconsideration of the major criteria “absence of venectasia” from the proposed diagnostic criteria, and propose that body asymmetry should be taken into consideration. Finally, the genetic research in this area is evolving, most recently with the identification of mutations in the GNA11 gene. Further studies should clarify whether molecular genetics should be part of the diagnostic process in the future.