Coffee and wine on the skin: A unique dermatological fusion

Dear Sir,

Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous disorder, first described by von Recklinghausen in 1881, characterized by caféaulait macules, axillary/inguinal freckling, neurofibromas, and Lisch iris nodules. It affects approximately 1 in 3,000 individuals worldwide and results from mutations in the NF1 gene on chromosome 17, encoding neurofibromin, a tumorsuppressor protein. Sturge–Weber syndrome (SWS), in contrast, is a sporadic neurocutaneous disorder defined by facial capillary malformations (portwine stains), leptomeningeal angiomatosis, seizures, ocular involvement, and cerebral calcifications.

The coexistence of NF1 and SWS is exceedingly rare, with only a small number of cases reported in the literature, beginning with two initial reports in 1979 and followed by additional isolated cases in 2008, 2013, and 2018.^[1-4]

A 32-year-old male laborer, born to second-degree consanguineous parents, presented with reddish raised lesions on the left side of the face associated with difficulty lifting the left eyelid. The facial lesion had been present since birth as a flat erythematous patch, which gradually thickened and developed a verrucous surface. He also reported multiple skincolored swellings on the trunk and extremities since childhood, recurrent seizures beginning at 7 years of age, and progressive visual decline in the left eye. There was no relevant family history.

Examination revealed a portwine stain over the left ophthalmic and maxillary divisions of the trigeminal nerve, multiple soft papules and nodules over the trunk and extremities, several caféaulait macules, axillary and palmar freckling, and bilateral Lisch nodules – fulfilling the diagnostic criteria for NF1 [Figure 1]. Magnetic resonance imaging of the brain showed leptomeningeal angiomatosis, cortical atrophy, and underlying calcifications over the left cerebral hemisphere, consistent with SWS, without intracranial neurofibromas. The coexistence of NF1 and SWS in this patient highlights a rare overlap of phakomatoses.

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Figure 1:

Multiple neurofibromas with café-au-lait macules over the trunk, along with a port-wine stain with surface nodularity on the left side of the face involving the ophthalmic and maxillary divisions of the trigeminal nerve

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NF1 is one of the phakomatoses – or neurocutaneous syndromes – which also include tuberous sclerosis complex, von Hippel–Lindau disease, and SWS.^[3] These conditions share overlapping features of cutaneous lesions and neurological involvement, although their genetic bases differ. Riccardi classified NF into eight types to reflect clinical heterogeneity.^[3]

Portwine stains (capillary malformations) are hallmark cutaneous findings of SWS, often following the distribution of the trigeminal nerve. They persist throughout life, may thicken with age, and can be associated with soft tissue or bony hypertrophy.^[4] Neurological manifestations of SWS, including seizures and developmental delay, correlate with leptomeningeal vascular malformations. Neuroimaging may reveal cerebral atrophy and gyriform calcifications, producing the classical “tramtrack” sign.^[5]

Srivastava et al. reported a rare cooccurrence of NF1 and SWS in a pediatric patient, highlighting several hypothesized mechanisms for this association: A chance cooccurrence due to the rarity of both conditions, shared embryologic vulnerabilities affecting neuroectodermal and mesodermal development, possible genetic or mosaic overlap wherein an NF1 mutation may create a permissive environment for vascular anomalies characteristic of SWS, and a “secondhit” somatic mutation superimposed on an inherited NF1 mutation leading to dual phenotypes.^[1-3] While the precise pathogenesis remains unclear, these hypotheses underscore the need for further research into the developmental and genetic interplay underlying neurocutaneous syndromes.

Our case emphasizes the importance of careful clinical evaluation in patients with neurocutaneous syndromes, as overlapping presentations may provide insights into common developmental or genetic mechanisms. Recognition of such rare dual associations is not only academically valuable but may also have implications for surveillance, counseling, and multidisciplinary management.

We present a rare case of coexistent NF1 and SWS, representing only the third such report to our knowledge. Continued reporting of overlapping neurocutaneous syndromes is essential to better delineate their relationships and guide further genetic and molecular research.