Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Pediatr Dermatol. 2024 Nov-Dec;41(6):1106-1113. doi: 10.1111/pde.15752. Epub 2024 Sep 10.
Focal dermal hypoplasia (FDH), also known as Goltz syndrome, is a rare ectodermal dysplasia that primarily affects the skin, skeleton, and eyes. It is an X-linked dominant disorder, predominantly seen in females, caused by pathogenic variants in PORCN.
We characterized a case series of four genetically confirmed FDH patients (three females, one male) at Aarhus University Hospital, Denmark. We estimated the FDH prevalence from our local cohort and nationwide registry data.
Three patients had characteristic dermatological findings suspicious for FDH and confirmed by targeted PORCN analysis. One patient had an atypical presentation with several malformations but only subtle skin changes and was diagnosed following trio exome-sequencing analysis. Skin atrophy with fat herniations and telangiectasias were typical cutaneous findings. Limb malformations included oligodactyly (cleft foot), syndactyly, and polydactyly. Eye abnormalities included coloboma and microphthalmos. Facial dysmorphology was defined by asymmetry, thin upper lip, and malformed ears. One patient developed a giant cell bone tumor, which is a rare feature of FDH. Dental findings included enamel hypoplasia with vertical grooving and irregular crowns. Four PORCN variants were identified, including three not previously reported in the literature.We estimated a regional point prevalence in Western Denmark of 1.6 cases per million population (95% confidence intervals (CI): 0.7-3.7 per million) and a nationwide registry-based point prevalence of 1.2 cases per million population (95% CI: 0.6-2.4 per million).
FDH is an extremely rare and complex multisystem disorder of variable presentation, which requires close multidisciplinary collaboration for diagnosis and patient care.
局灶性真皮发育不良（FDH），也称为 Goltz 综合征，是一种罕见的外胚层发育不良，主要影响皮肤、骨骼和眼睛。它是一种 X 连锁显性遗传疾病，主要见于女性，由 PORCN 中的致病变异引起。
我们对丹麦奥胡斯大学医院的四例经基因证实的 FDH 患者（三女一男）进行了病例系列分析。我们根据当地队列和全国登记数据估计了 FDH 的患病率。
三名患者具有特征性的皮肤科表现，怀疑为 FDH，并通过靶向 PORCN 分析得到证实。一名患者表现不典型，有多种畸形，但仅有轻微的皮肤改变，经 trio 外显子组测序分析后诊断。皮肤萎缩伴脂肪疝和毛细血管扩张是典型的皮肤表现。肢体畸形包括并指（裂足）、并指和多指。眼部异常包括眼眶和小眼球。面部畸形表现为不对称、薄上唇和畸形耳。一名患者发生了罕见的骨巨细胞瘤。牙齿表现包括釉质发育不全伴垂直沟和不规则牙冠。共发现 4 种 PORCN 变异，其中 3 种以前未在文献中报道。我们估计在丹麦西部的区域患病率为每百万人口 1.6 例（95%置信区间（CI）：0.7-3.7 例/百万），基于全国登记的患病率为每百万人口 1.2 例（95%CI：0.6-2.4 例/百万）。
FDH 是一种极其罕见且复杂的多系统疾病，表现多样，需要多学科密切合作进行诊断和患者护理。
