Recognizing Mandibular Hypoplasia, Deafness, Progeroid Features, and Lipodystrophy Syndrome Through Its Cutaneous...

Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL) is an extremely rare autosomal dominant progeroid disorder caused by pathogenic variants in POLD1. Because MDPL shares many clinical features with Werner syndrome (WS), distinguishing between the two disorders can be challenging. We report a Japanese man with genetically confirmed MDPL caused by the recurrent POLD1 p.Ser605del variant, highlighting its distinctive cutaneous manifestations. The patient exhibited mandibular hypoplasia, limb-predominant lipodystrophy, skin atrophy, painful plantar clavi and calluses, and later developed prominent telangiectasias. Radiographs at the initial presentation revealed multiple extraosseous calcifications in the lower leg, followed by the development of a refractory skin ulcer over the same calcified region. Computed tomography confirmed calcifications within the subcutaneous tissue and skeletal muscle. To our knowledge, soft-tissue calcification and refractory skin ulceration have not previously been reported in MDPL. Although MDPL shares substantial clinical overlap with WS, it can be distinguished by its earlier onset, preserved scalp hair, prominent telangiectasias, sensorineural hearing loss, an absence of cataracts, and a lack of a recognized predisposition to malignancy. This case expands the cutaneous spectrum of MDPL and emphasizes the dermatological clues that facilitate its differentiation from WS.