Extracutaneous manifestations in phacomatosis cesioflammea and cesiomarmorata: Case series and literature review

Abstract

Phacomatosis pigmentovascularis (PPV) comprises a family of rare conditions that feature vascular abnormalities and melanocytic lesions that can be solely cutaneous or multisystem in nature. Recently published work has demonstrated that both vascular and melanocytic abnormalities in PPV of the cesioflammea and cesiomarmorata subtypes can result from identical somatic mosaic activating mutations in the genes GNAQ and GNA11. Here, we present three new cases of PPV with features of the cesioflammea and/or cesiomarmorata subtypes and mosaic mutations in GNAQ or GNA11. To better understand the risk of potentially occult complications faced by such patients we additionally reviewed 176 cases published in the literature. We report the frequency of clinical findings, their patterns of co-occurrence as well as published recommendations for surveillance after diagnosis. Features assessed include: capillary malformation; dermal and ocular melanocytosis; glaucoma; limb asymmetry; venous malformations; and central nervous system (CNS) anomalies, such as ventriculomegaly and calcifications. We found that ocular findings are common in patients with phacomatosis cesioflammea and cesiomarmorata. Facial vascular involvement correlates with a higher risk of seizures (p = .0066). Our genetic results confirm the role of mosaic somatic mutations in GNAQ and GNA11 in phacomatosis cesioflammea and cesiomarmorata. Their clinical and molecular findings place these conditions on a clinical spectrum encompassing other GNAQ and GNA11 related disorders and inform recommendations for their management.

Keywords: GNA11; GNAQ; management; phacomatosis cesioflammea; phacomatosis cesiomarmorata; phacomatosis pigmentovascularis.

Figure 1:

An 11-year-old boy with phacomatosis cesioflammea, characterized by dermal melanocytosis and nevus flammeus. Capillary malformation on his right face and neck (a,b). Hyperpigmentation noted on his central palate (c) and sclera of his right eye (d). Additional capillary malformations on his right flank, legs and feet (e-g). MR imaging demonstrated absence of multiple deep veins including bilateral iliacs, infrarenal vena cava and right axillary vein (h).

Figure 2:

A 1-year-old male with phacomatosis cesioflammea, characterized by dermal melanocytosis and capillary malformation/nevus flammeus. Capillary vascular changes on the upper torso (a), face (c), and extremities (a, e). Hypermelanosis on the abdomen (a), back (b), and legs (e). Facial differences include prominent forehead, upturned nasal tip, tented upper lip (c), and a pre-auricular ear tag (d). MR imaging showed unusual veins with marked asymmetry, diminutive sagittal, sigmoid, and transverse sinuses. The right jugular vein was not seen (f).

Figure 3:

A 17 month old male with phacomatosis pigmentovascularis with features of cesioflammea and cesiomarmorata types. Cutis marmorata and diffuse capillary malformation with overlapping areas of dermal melanocytosis at initial evaluation at 2 weeks of age (a). Capillary malformation involving much of the face, torso and thighs with prominent melanocytosis of the upper thighs at 12 months of age (b, c) Faded appearance of capillary malformations after several rounds of pulsed dye laser treatments. Axial T2 weighted MRI of the brain showing a right front developmental venous anomaly (DVA) (f) as well as a likely DVA in the left temporal region and quadrigeminal cistern (g).