Herlin Laura Krogh, Schmidt Sigrun Alba Johannesdottir, Mogensen Trine H, Sommerlund Mette
Department of Dermatology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 67, Aarhus N, 8200, Denmark.
Department of Clinical Medicine, Aarhus University, Building A, Palle Juul-Jensens Boulevard 99, Aarhus N, Denmark.
Orphanet J Rare Dis. 2024 Dec 2;19(1):454. doi: 10.1186/s13023-024-03480-8.
Incontinentia pigmenti (IP) is an X-linked dominant multisystemic disorder caused by pathogenic variants in the IKBKG gene. Population-based research into the epidemiology of IP is lacking.
This nationwide cross-sectional study from Jan 1st, 1995 to August 25th, 2021, searched the Danish National Patient Registry (DNPR), the Danish National Database of Rare Genetic Diseases (RareDis) and the Danish Genodermatosis Database to identify patients recorded with a diagnosis of IP. This search was followed by diagnosis validation and collection of clinical data from patient medical records. We investigated the clinical characteristics and genetics of the final cohort of validated IP cases. We estimated the point prevalence in the Danish population, based on non-deceased IP patients currently living in Denmark. Furthermore, we estimated the birth prevalence from 1995 to 2020, assuming a diagnostic delay of up to six months.
We identified a validated cohort of 75 IP patients, including 71 (94.7%) females and 4 (5.3%) males. We estimated a birth prevalence of 2.37 (95% CI: 1.74-3.25) per 100,000 or 1 in 42,194. A total of 54 (72%) patients had a genetic diagnosis, including 39 (72.2%) with the recurrent exon 4-10 deletion and 10 (18.5%) with point mutations in IKBKG. A positive family history was reported in 53.3%. Besides the recognizable blaschkolinear skin lesions reported in 70 (93.3%) of the patients, commonly reported manifestations included the involvement of the teeth (58.7%), the central nervous system (30.7%), hair (26.7%), and eyes (22.6%), as well as nail dystrophy (16.0%).
We identified and characterized a nationwide population-based cohort of IP patients and report a birth prevalence of 2.37 per 100,000 live births, which is twice as high as previous estimates.
色素失禁症（IP）是一种由IKBKG基因的致病变异引起的X连锁显性多系统疾病。目前缺乏基于人群的IP流行病学研究。
这项从1995年1月1日至2021年8月25日的全国性横断面研究，检索了丹麦国家患者登记处（DNPR）、丹麦国家罕见遗传病数据库（RareDis）和丹麦遗传性皮肤病数据库，以确定记录有IP诊断的患者。在检索之后，进行诊断验证并从患者病历中收集临床数据。我们调查了最终经确认的IP病例队列的临床特征和遗传学情况。我们根据目前居住在丹麦的未死亡IP患者，估计了丹麦人群中的点患病率。此外，我们假设诊断延迟长达6个月，估计了1995年至2020年的出生患病率。
我们确定了一个由75名IP患者组成的经确认队列，其中包括71名（94.7%）女性和4名（5.3%）男性。我们估计出生患病率为每10万人中2.37例（95%置信区间：1.74 - 3.25），即42194人中1例。共有54名（72%）患者进行了基因诊断，其中39名（72.2%）存在外显子4 - 10重复缺失，10名（18.5%）在IKBKG基因中有点突变。53.3%的患者有阳性家族史。除了70名（93.3%）患者报告有可识别的沿Blaschko线分布的皮肤病变外，常见的表现还包括牙齿受累（58.7%）、中枢神经系统受累（30.7%）、毛发受累（26.7%）、眼睛受累（22.6%）以及指甲营养不良（16.0%）。
我们识别并描述了一个基于全国人群的IP患者队列，并报告出生患病率为每10万活产儿中2.37例，这是先前估计值的两倍。
