Birt-Hogg-Dubé syndrome in a patient with localized fibrofolliculomas and a novel mutation in the FLCN gene.

BACKGROUND

Birt-Hogg-Dubé syndrome (BHDS) is characterized by skin fibrofolliculomas (FF), multiple lung cysts, spontaneous pneumothorax, and renal cancer. Cutaneous lesions are usually distributed over the face, neck, and upper trunk. The presence of FF confined to a circumscribed region of the skin has rarely been reported.

CASE REPORT

A 64-year-old woman presented with a 20-year history of asymptomatic skin lesions located on the neck. Multiple skin-colored papules with a clinical plaque-like appearance were confined to the right side of the neck. Histopathological findings were typical for FF, and BHDS was suspected. The novel heterozygous mutation p.Val126SerfsX4 was identified in exon 5 of the FLCN gene. Colonoscopy, abdominal ultrasound, and abdominal thoracic scan revealed no associated pathologies, except for benign renal and hepatic cysts.

DISCUSSION

To date, only two cases of localized FF in BHDS have been reported. Mutation analysis was not performed, but the authors considered the lesions to represent a localized variant of BHDS and speculated that this unusual form of the disease may be associated with a lack of visceral involvement as no signs of systemic disease were detected.

CONCLUSIONS

We identified the novel germline mutation p.Vall26SerfsX4 as responsible for this aspect of the patient's phenotype, which suggests that alterations in the FLCN gene are also responsible for localized forms of BHDS. Moreover, the localized distribution of skin lesions may be related to a less severe form of the disease.