A case of Schöpf-Schulz-Passarge syndrome presented with widespread apocrine hidrocystomas showing variable clinical...

Dear Editor, Genodermatoses are usually diagnosed in early childhood but diagnosis may be delayed in rare cases. Schöpf-Schulz-Passarge syndrome (SSPS) first described in 1971 is a rare type of autosomal recessive ectodermal dysplasia characterized by palmoplantar keratoderma, periocular and eyelid apocrine hidrocystomas, hypodontia, hypotrichosis, and nail dystrophy (1). Fewer than 40 cases have been reported up to 2018 (2) and the number has slightly increased with subsequent case reports. We report here a 73-year-old male patient whose parents were third-degree cousins presented to dermatology clinic for symptomatic palmoplantar hyperkeratosis (Figs 1a-1b) with a 30-years history. Physical examination determining mild alopecia (Fig. 1c), dental loss (Fig. 1d), micronychia (Figs 1e-1f) in association with numerous cystic lesions suggested the diagnosis of SSPS. Remarkably numerous hidrocystomas localized to the eyelids, periocular area, cheeks, nose, forehead, ears, shoulders, supraclavicular and axillary region showed three distinct morphologies; milia-like yellowish (Fig. 2a), bluish dome-shaped (Figs 2a-2b, 2d) and translucent (Fig. 2c) papular lesions. The histopatological examination determining the diagnosis of apocrine hidrocystoma (Figs 2e-2f) was followed by genetic confirmation of SSPS. A homozygous c.391G>A (p.Ala131Thr) variant was identified in WNT10A by Clinical Exome Sequencing. According to American College of Medical Genetics and Genomics criteria (3), this variant was classified as pathogenic (PS4, PM1, PM2, PM5, PP3, PP5). Rarely reported findings of SSPS including facial dysmorphism, loss of body hair (Fig. 2d), localized hyperhidrosis (Fig. 1f), generalized hypohidrosis, and atrophic tongue (Fig. 1d) was also associated. However, other rare supporting features, such as eccrine syringofibroadenoma, rosacea-like facial erythema, hypoplastic areolae and nipple, and ocular involvement were not observed (4-7). The patient had also a basal cell carcinoma on the nose (Fig. 2c) which has been occasionaly reported in SSPS (4). Furthermore, a 9 × 9 cm soft, subcutaneous mass located on the midline of the lumbar region, clinically suggestive of a lipoma, was also noted. In our case, although dental loss was the earliest presenting feature, major manifestations such as periocular and eyelid apocrine hidrocystomas and palmoplantar keratoderma emerged initially after the 5th decade, leading to a delay in diagnosis. Whereas extraocular localizations of apocrine hidrocystoma is described in sporadic cases (8), it has not been highlighted in the context of SSPS. Our patient, however, exhibited numerous lesions in multiple additional sites including the nose, cheeks, forehead, external ears, upper trunk and axillae, broadening the recognized clinical distribution of this hallmark finding. A noteworthy finding in this patient was the concurrent presence of three morphologically distinct types of facial apocrine hidrocystomas. While a review of previously reported cases revealed that lesions with different morphologies can coexist in individual patients (2), this phenotypic diversity has rarely been explicitly highlighted in the literature. WNT10A mutations, inherited in an autosomal recessive manner, have been documented in both homozygous and compound heterozygous states (7, 9). These mutations can result in a wide phenotypic spectrum, ranging from isolated hypodontia and oligodontia to more complex ectodermal dysplasia syndromes such as odonto-onycho-dermal dysplasia (OODD) and SSPS (5, 6, 9). On the other hand some authors suggest that these two conditions may represent phenotypic variations of the same underlying genetic defect rather than distinct entities (10). While our patient exhibited overlapping features with OODD, including hypodontia, palmoplantar hyperkeratosis, hypotrichosis, and nail dystrophy, the presence of numerous apocrine hidrocystomas was distinctive for SSPS (5)D. In conclusion, SSPS can be recognized even decades after onset of the mild dermatological manifestations (2). Awareness of the rich clinical spectrum of apocrine hidrocystomas as they are not limited to eyelids or periocular area and present with papulonodules in different size and color may be crucial (5)D. Although a therapeutic option for SSPS still does not exist timely recognition may prevent unnecessary diagnostic and therapeutic interventions and enable appropriate genetic counseling of the family members.