Cutis Marmorata Telangiectatica Congenita

Clinical Features

Van Lohuizen (1922) described a child with livedo reticularis, telangiectases, and superficial ulceration. Way et al. (1974) found that all reported cases had been sporadic. Andreev and Pramatarov (1979) reported 2 adult sisters with CMTC. Onset was at birth in both. One developed hypertension at age 16 years.

Kurczynski (1982) described the case of a 4-year-old girl whose father and paternal grandmother were said to be identically affected in childhood with improvement by adulthood. Robinow (1985) saw 2 cases of CMTC in seemingly unrelated children of German ancestry living near each other in Ohio.

Shields et al. (1990) described a female child in whom CMTC was associated with congenital bilateral total retinal detachments and secondary neovascular glaucoma. Retinal detachments produced bilateral leukocoria simulating retinoblastoma.

In a report of a patient with CMTC who also had congenital hypothyroidism, Pehr and Moroz (1993) noted that two-thirds of patients with CMTC have other associated anomalies. Lingier et al. (1992) reported 4 cases with prominent phlebectasia. Dutkowsky et al. (1993) reported leg-length discrepancies, and Kennedy et al. (1992) noted that 2 patients had a short leg that was also thinner. They also reported associated tendinitis stenosans (stenosing tendinitis) and bowing of the lower legs.

Toriello et al. (1988) described CMTC in association with Adams-Oliver syndrome (100300).

Ben-Amitai et al. (2001) noted that fewer than 300 cases of CMTC had been reported in the world literature. The first association of CMTC with congenital anomalies, namely, Sturge-Weber syndrome (185300) and patent ductus arteriosus (607411), was described by Petrozzi et al. (1970). Associated malformations are thought to occur in approximately 20 to 40% of affected individuals (Picascia and Esterly, 1989; Devillers et al., 1999; Ben-Amitai et al., 2000). Ben-Amitai et al. (2001) reported the occurrence of hypospadias in 4 patients in a series of 52 Israeli males with CMTC (7.69%), which is more than 13 times the rate of isolated hypospadias in this population. Ben-Amitai et al. (2001) suggested that hypospadias may be an associated noncutaneous feature of CMTC.

Torrelo et al. (2003) reported 2 patients with an unusual association of extensive cutis marmorata telangiectatica congenita and aberrant mongolian spots. They asserted that this association is best explained as a phenomenon of nonallelic twin spotting and suggested that this condition may be a novel variant form of phacomatosis pigmentovascularis.

Hinek et al. (2008) reported a 16-month-old boy with CMTC and generalized vascular abnormalities. At birth, he had multiple bluish-red reticulated bands scattered over the entire skin surface and associated with ulcerations. Dilated veins over the face, scalp, and abdomen were also noted. After 2 to 3 months, the ulcerations had healed well, while the bluish-red reticulated marks and the dilated veins persisted. He had a retinal bleed at age 7 months, and showed developmental delay, seizures, and extensive periventricular white matter calcifications on brain imaging. At 14 months, he was found to have severe pulmonary hypertension with significant tricuspid insufficiency and right heart failure. An open lung biopsy demonstrated marked hyperplasia of medial smooth muscle and small pulmonary arteries. He died at age 20 months from persistent severe hypoxemia. Postmortem examination showed abnormal pulmonary arteries and veins, with irregular thick elastic lamina in the media. Laboratory studies showed increased blood copper levels. Studies of dermal fibroblasts from the patient showed normal tropoelastin (ELN; 130160) synthesis, but decreased deposition of mature elastic fibers that appeared to result from heightened elastolysis. Further studies indicated that the increased elastolysis was due to copper-dependent inactivation of alpha-1-antitrypsin (PI; 107400). The cells also produced more reactive oxygen species. Hinek et al. (2008) suggested that a high level of free copper in this patient was a major triggering factor contributing to the development of the CMTC phenotype.

Molecular Genetics

Associations Pending Confirmation

For discussion of a possible association between variation in the ARL6IP6 gene and cutis marmorata telangiectatica congenita, see 616495.0001.