Uncombable hair syndrome and atypical clonal nevus presentation in a VACTERL syndrome patient

A 7-year-old Caucasian girl was referred to dermatology for evaluation of a mole on the back with recent onset of irregular pigmentation. Past medical history was significant for VACTERL syndrome with associated cardiac, GU, and nervous system anomalies. Physical examination revealed a 5 mm light brown macule on the upper back with two distinct black foci, one located centrally and the other located eccentrically. A shave biopsy of the nevus was performed, revealing a proliferation of junctional and intradermal melanocytic nests. The cells lacked pigment superficially but demonstrated deeper extension of epithelioid melanocytes with dense cytoplasmic melanin and multiple melanophages. Cytologic atypia and mitoses were absent. The patient received a diagnosis of an inverted type A nevus (clonal nevus) and reassurance. The patient was also incidentally noted to have unruly blonde hair which would not lay flat. A hair clipping was sent to dermatopathology for microscopic examination. The hairs were embedded in paraffin and cut across the short axis, revealing irregular cross-sections consisting of reniform and triangular shapes. Genetic testing identified two pathogenic variants in the PADI3 gene, consistent with autosomal recessive PADI3-related uncombable hair syndrome. The coexistence of a clonal nevus and uncombable hair syndrome is a previously undescribed presentation. Furthermore, two distinct foci of hyperpigmentation within the patient's nevus are also unusual, as clonal nevi typically present with a single eccentric or central focus of blue-black or blue-gray pigmentation.