Clinical characteristics: Isolated and classic cutis marmorata telangiectatica congenita (CMTC) are characterized by congenital skin changes including erythematous-to-violaceous, reticulated, net-like or marbled-appearing patches of skin that do not mostly or completely resolve with warming or any other acute intervention. Individuals with isolated CMTC have no other syndromic features, and skin lesions tend to fade or resolve. Those with classic CMTC may have accompanying hemihypoplasia with body asymmetry, skin atrophy or ulceration, other vascular malformations, and occasional ocular issues (early-onset glaucoma and/or peripheral retinal vascular attenuation) but do not have other malformations, dysmorphic features, or cognitive impairment. The most common location for the CMTC lesions is on the legs. An affected limb may also display weakness or be unusually susceptible to cold compared to an unaffected limb. In more than half of affected individuals, skin lesions will generally fade across a wide range in age (6 weeks to 26 years), most commonly in the first year of life, but may not resolve completely.

Diagnosis/testing: A molecular diagnosis can be established in a proband with suggestive cutaneous findings if a mosaic heterozygous pathogenic variant in GNA11 is identified by molecular genetic testing.

Management: Treatment of medical manifestations: Most cutaneous changes improve or resolve with time and do not require intervention. Serial exams with photography are helpful. Persistent CMTC vascular lesions may be addressed with frequency-doubled Nd:YAG, Q-switched alexandrite, and pulsed dye laser therapy, although outcomes are mixed depending on the severity and depth of the lesions. Skin ulceration is usually treated by a qualified ulcer team with advanced knowledge in pain control. Intense pulsed light therapy may be considered to aid in ulcer improvement and faster healing. Lumbar sympathetic blockade may be considered for those with chronic pain and temperature dysregulation. Shoe lifts or orthotics may be considered in those with mild leg length discrepancies, and epiphysiodesis or limb lengthening may be considered in severe cases. Weakness is typically addressed through physical therapy. Standard treatment per ophthalmologist for glaucoma and peripheral retinal vascular abnormalities is recommended.

Treatment of psychosocial issues: Parents should be counseled on how to deal with child abuse accusations that may occur when individuals (including care providers and strangers) who are not familiar with CMTC happen to see their child's skin lesions. Self-esteem issues can be a major problem for affected individuals and may be addressed proactively through resiliency training and bibliotherapy. People unfamiliar with the condition are often worried that the condition may be contagious, so providing this information up front can defuse unwanted curiosity.

Surveillance: Close monitoring of the skin for early signs of impending ulceration as determined at initial evaluation; assessment for pain, weakness, and temperature dysregulation at each visit; annual monitoring of limb lengths and girth until skeletal maturity; ophthalmologic evaluation to include measurement of intraocular pressure and consideration of peripheral retinal vascular imaging every six months for the first four years of life, then annually (throughout lifetime) or any time there is ocular pain or visible corneal clouding; annual monitoring of coping skills related to visible physical differences starting at school age.

Agents/circumstances to avoid: Blood draws or IV placement in an affected limb; cold exposure.

Genetic counseling: Isolated and classic CMTC are typically not inherited. Most affected individuals represent simplex cases.

1. Vertical transmission of a GNA11 pathogenic variant has not been reported to date. The risk to sibs of a proband with somatic mosaicism for a pathogenic variant in GNA11 would be expected to be the same as in the general population.

2. Rarely, autosomal dominant inheritance has been reported in families with a clinical diagnosis of isolated or classic CMTC (i.e., families in which a GNA11 pathogenic variant has not been identified). Sib recurrence in families with a clinical diagnosis of isolated or classic CMTC has been described but is very rare.

Because vertical transmission of a mosaic GNA11 pathogenic variant has not been reported to date and clinically diagnosed isolated and classic CMTC is usually not inherited, risk to family members is presumed to be very low.