Dowling Degos disease (DDD) is a rare autosomal dominant genodermatosis characterized by acquired, slowly progressive reticulated pigmented lesions primarily involving flexural skin areas. Mutations in KRT5, POGLUT-1 and POFUT-1 genes have been associated with DDD, and loss-of-function mutations in PSENEN, a subunit of the gamma-secretase complex, were found in patients presenting with DDD or DDD comorbid with hidradenitis suppurativa (HS). A nonsense mutation in NCSTN, another subunit of the gamma-secretase, was already described in a patient suffering from HS and DDD but whether NCSTN could be considered a novel gene for DDD is still debated. Here, we enrolled a four-generation family with HS and DDD. Through Whole Exome Sequencing (WES) we identified a novel nonsense mutation in the NCSTN gene in all the affected family members. To study the impact of this variant, we isolated outer root sheath cells from patients\' hair follicles. We showed that this variant leads to a premature stop codon, activates a nonsense-mediated mRNA decay, and causes NCSTN haploinsufficiency in affected individuals. In fact, cells treated with gentamicin, a readthrough agent, had the NCSTN levels corrected. Moreover, we observed that this haploinsufficiency also affects other subunits of the gamma-secretase complex, possibly causing DDD. Our findings clearly support NCSTN as a novel DDD gene and suggest carefully investigating this co-occurrence in HS patients carrying a mutation in the NCSTN gene.

Haber\'s syndrome is an autosomal dominant, rare genodermatosis characterized by photosensitive, persistent facial erythema associated with reticulated hyperpigmentation. We present a case of an eight-year-old healthy Saudi girl who presented with facial erythema and generalized reticulated hyperpigmentation. Systematic review and laboratory studies were unremarkable. Histopathological examination revealed hyperpigmentation of the basilar keratinocytes with mild digitated elongations of the rete ridges. The patient was diagnosed with early-onset clinical presentation of Haber\'s syndrome. In this report, Haber\'s syndrome is reviewed, and differential diagnoses of reticulated hyperpigmentation are discussed.

Acquired dermal macular hyperpigmentation (ADMH) is a recently coined term to encompass lichen planus pigmentosus (LPP), erythema dyschromicum perstans (EDP), and Riehl\'s melanosis. Here we report a 60 -year- old female, with an insignificant past medical history, who presented to the dermatology clinic, with slightly itchy skin lesions on her body. The lesions were slowly increasing in number over the last 10 years. The patient was otherwise healthy and was not taking any medications. A review of systems was unremarkable. There was no similar case in the family and the parents did not show consanguinity. Skin examination revealed multiple well-defined non-scaly brownish macules scattered on her body. In addition, bilateral macules and papules were present in the inframammary folds. There were no skin lesions in the axillae, groin, and intergluteal folds. Differential diagnoses include Dowling Degos Disease (DDD), LPP, and EDP. A 4 mm punch skin biopsy was taken from skin lesions under the breast. It revealed hyperkeratosis, hypergranulosis, and acanthosis. The dermis showed a band-like infiltrate of mononuclear histiocytic cellular infiltrate with basal layer degeneration. According to the above clinicopathological findings, the diagnosis of lichen planus was made. The patient was reassured. She was started on hydroxychlorquine 200 mg tab bid, a topical steroid, and topical calcineurin inhibitors, and was asked to follow up regularly in the dermatology clinic.

Reticulate hyperpigmentary disorders are a group of rare genetic pigmentary abnormalities which includes reticulate acropigmentation of Kitamura (RAPK), Dowling-Degos disease (DD), reticulate acropigmentation of Dohi (RAPD), Haber\'s syndrome, and Galli-Galli disease. A 25-year-old male presented with asymptomatic dark-colored lesions on his hands and feet with light-colored skin lesions involving the trunk since three years. Dermatological examination revealed hyperpigmented macules in a reticulate pattern involving the dorsa of the hands and feet, front and sides of the neck, axillae, periorbital region, and groin. Multiple pits were present over both palms, with breaks in dermatoglyphics. He also had multiple nonacne facial scars predominantly on the nose and malar areas. The patient had overlapping features of RAPK and DDD. In addition, he also had hypopigmented macules and acneiform facial scars. Such an overlap of features of reticulate pigmentation has not been previously reported in the literature.