Vasconcelos Alice P, Nogueira Ana, Matos Pedro, Pinto Joel, Pinho Maria João, Fernandes Susana, Dória Sofia, Pinto Moura Carla
Medical Genetics Service, Centro Hospitalar Universitário de São João (CHUSJ) EPE, Porto, Portugal.
Department of Dermatology and Venereology, Centro Hospitalar Universitário de São João (CHUSJ) EPE, Porto, Portugal.
Eur J Med Genet. 2023 Oct;66(10):104827. doi: 10.1016/j.ejmg.2023.104827. Epub 2023 Aug 30.
Autosomal recessive keratitis-ichthyosis-deafness syndrome (KIDAR MIM #242150) is a very rare disorder caused by pathogenic loss-of-function variants in the AP1B1 gene. So far, nine patients have been reported in the literature and more clinical descriptions are essential to further delineate the phenotype of KIDAR. Here we report a new patient with KIDAR and compare the clinical findings with those from the other published cases with molecular confirmation. We describe a 14-year-old male born to non-consanguineous parents with unremarkable family history. The patient had fetal ascites, neonatal pancreatic insufficiency with consequent failure to thrive, feeding difficulties, recurrent infections and sepsis. The skin examination was remarkable for an ichthyosis with conspicuous palmoplantar keratoderma, sparse and brittle hair with alopecia on the vertex and slight bilateral ectropion. He had short stature, thin build, frontal bossing, small teeth and prominent abdomen. Additional features were congenital profound bilateral sensorineural deafness, photosensitivity and photophobia. Mild global developmental delay was noted. Persistent mild anemia, neutropenia, thrombocytopenia, and low serum copper, ceruloplasmin and growth hormone were also present. Brain magnetic resonance imaging (MRI) showed cerebral atrophy and thin corpus callosum. Genetic testing revealed a homozygous deletion in the AP1B1 gene, possibly including the same exons as a previously reported deletion. Comparing the phenotypes of all reported individuals, they are highly concordant and major features are enteropathy with feeding difficulties, failure to thrive, ichthyosis, palmoplantar keratoderma, sensorineural deafness and sparse and brittle hair. Here we report other features present in more than one patient that could be part of the phenotypic spectrum and suggest copy number variation analysis to be performed alongside sequencing of the AP1B1 gene in case of suspicion.
常染色体隐性遗传性角膜炎-鱼鳞病-耳聋综合征（KIDAR，MIM编号#242150）是一种非常罕见的疾病，由AP1B1基因的致病性功能丧失变异引起。迄今为止，文献中已报道了9例患者，更多的临床描述对于进一步明确KIDAR的表型至关重要。在此，我们报告1例新的KIDAR患者，并将临床发现与其他经分子确诊的已发表病例进行比较。我们描述了一名14岁男性，其父母非近亲结婚，家族史无异常。该患者有胎儿腹水、新生儿胰腺功能不全，继而出现生长发育迟缓、喂养困难、反复感染和败血症。皮肤检查发现有鱼鳞病，伴有明显的掌跖角化病，头发稀疏且脆弱，头顶脱发，双侧轻度睑外翻。他身材矮小、体型消瘦、额头突出、牙齿小且腹部突出。其他特征包括先天性双侧重度感音神经性耳聋、光敏性和畏光。存在轻度全面发育迟缓。还存在持续性轻度贫血、中性粒细胞减少、血小板减少以及血清铜、铜蓝蛋白和生长激素水平低。脑磁共振成像（MRI）显示脑萎缩和胼胝体变薄。基因检测显示AP1B1基因存在纯合缺失，可能包括与先前报道的缺失相同的外显子。比较所有已报道个体的表型，它们高度一致，主要特征为伴有喂养困难的肠病、生长发育迟缓、鱼鳞病、掌跖角化病、感音神经性耳聋以及头发稀疏且脆弱。在此我们报告了不止1例患者出现的其他特征，这些特征可能是表型谱的一部分，并建议在怀疑时除了对AP1B1基因进行测序外，还应进行拷贝数变异分析。
