通过皮肤表现识别下颌骨发育不全、耳聋、早老样特征和脂肪营养不良综合征：与Werner综合征的鉴别

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中文摘要

下颌骨发育不全、耳聋、早老样特征和脂肪营养不良综合征（MDPL）是一种极其罕见的常染色体显性早老样疾病，由POLD1致病性变异引起。由于MDPL与Werner综合征（WS）有许多共同的临床特征，区分这两种疾病可能具有挑战性。我们报告一名经基因确诊的日本男性MDPL患者，由复发性POLD1 p.Ser605del变异所致，重点介绍其独特的皮肤表现。该患者表现为下颌骨发育不全、以四肢为主的脂肪营养不良、皮肤萎缩、疼痛性足底鸡眼和胼胝，随后出现明显的毛细血管扩张。初诊时的X线片显示小腿多发骨外钙化，随后在同一钙化区域出现难治性皮肤溃疡。计算机断层扫描证实皮下组织和骨骼肌内存在钙化。据我们所知，软组织钙化和难治性皮肤溃疡此前尚未在MDPL中被报道。尽管MDPL与WS有大量临床重叠，但可通过其发病更早、头皮毛发保留、明显的毛细血管扩张、感音神经性听力损失、无白内障以及缺乏公认的恶性肿瘤易感性来区分。本病例扩展了MDPL的皮肤表现谱，并强调了有助于其与WS鉴别的皮肤病学线索。

英文摘要

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.