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

GNA11 brain somatic pathogenic variant in an individual with phacomatosis pigmentovascularis

“…In addition, GNA11 somatic variants can cause a range of cutaneous disorders with or without extracutaneous manifestations that are not fully understood. 6 Thus, our patient may represent the severe end of the spectrum of neurologic features in GNA11 -related disorders.…”

“…Epilepsy and other neurologic features have been described in PPV, although the extent and severity at cohort level are not well documented. 3,4,6 On the other hand, life-threatening seizures such as apneic seizures are observed in the closely related SWS. 5 However, our patient only had cutaneous signs of PPV with intracranial involvement, and no evidence for leptomeningeal angiomatosis or facial capillary malformation, typically seen in SWS, was found.…”

“…3 Reported CNS features are similar but not identical to those described in the closely related Sturge-Weber syndrome (SWS) and include seizures, global developmental delay (GDD), intellectual disability, cortical atrophy, asymmetric hemispheres, intracranial hypertension, hydrocephalus, ventriculomegaly, brain calcifications, abnormal EEG, congenital hearing loss, and spina bifida. 3–6 Because of the rarity of PPV and the multiple subtypes, the neurologic features have not been extensively characterized.…”

Phakomatosis pigmentovascularis IIb (phakomatosis cesioflammea) associated with the absence of infrarenal inferior vena cava

“…His skin lesions showed both checkerboard and phylloid patterns of mosaicism and various vascular anomalies including AIVC. The absence of IVC has been rarely reported in a patient with phacomatosis cesiomarmorata 2 and a patient with overlapping features of cesiomarmorata and cesioflammea 3 …”

Phacomatosis spilorosea versus phacomatosis melanorosea: a critical reappraisal of the worldwide literature with updated classification of phacomatosis pigmentovascularis

“…The latter is now firmly established as the more appropriate one. Phacomatosis cesioflammea (nevus cesius [NC] associated with nevus flammeus) is by far the most commonly observed type, with hundreds of cases reported to date (5). Phacomatosis cesiomarmorata (NC associated with cutis marmorata telangiectatica congenita) is probably the second most common PPV, as testified by a couple of dozen cases identified in reviews that considered PubMed® only (5,6).…”