Matsuura Nobuo, Kaname Tadashi, Niikawa Norio, Ooyama Yoshihide, Shinohara Osamu, Yokota Yukifumi, Ohtsu Shigeyuki, Takubo Noriyuki, Kitsuda Kazuteru, Shibayama Keiko, Takada Fumio, Koike Akemi, Sano Hitomi, Ito Yoshiya, Ishikura Kenji
Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Japan.
Department of Genome Medicine, National Research Institute for Child Health and Development, Tokyo, Japan.
Endocr Connect. 2022 Sep 22;11(10). doi: 10.1530/EC-22-0151. Print 2022 Oct 1.
This study aimed to report on 15 Japanese patients with acrodysostosis and pseudohypoparathyroidism (PHP) and analyze them using the newly proposed classification of the EuroPHP network to determine whether this classification system is suitable for Japanese patients.
We divided the patients into three groups based on hormone resistance, the number of fingers with short metacarpals, the existence of cone-shaped epiphyses and gene defects.
We carried out clinical, radiological and genetic evaluations of two patients in group A (iPPSD5), six patients in group B (iPPDS4) and seven patients in group C (iPPSD2).
Group A consisted of two siblings without hormone resistance who had the most severe bone and physical developmental delays. PDE4D gene defects were detected in both cases. Group B consisted of six patients who showed hormone resistance without hypocalcemia. Short metacarpal bones with corn-shaped epiphyses were observed in all patients. In two cases, PRKAR1A gene defects were detected; however, their clinical and radiological features were not identical. The facial dysmorphism and developmental delay were less severe and PRKAR1A gene defects were detected in case B-3. Severe facial dysmorphism and deformity of metacarpal bones were observed, but no gene defect was detected in case B-1. Group C consisted of seven patients with PHP1a, four of whom had maternally inherited heterozygous inactivating mutations in one of the GNAS genes. The clinical and radiological features of the patients in group C were not identical either.
The newly proposed classification is suitable for Japanese patients; however, heterogeneities still existed within groups B and C.
本研究旨在报告15例患有肢端发育不全和假性甲状旁腺功能减退症（PHP）的日本患者，并使用欧洲PHP网络新提出的分类方法对其进行分析，以确定该分类系统是否适用于日本患者。
我们根据激素抵抗、掌骨短小的手指数量、锥形骨骺的存在以及基因缺陷将患者分为三组。
我们对A组（iPPSD5）的2例患者、B组（iPPDS4）的6例患者和C组（iPPSD2）的7例患者进行了临床、放射学和遗传学评估。
A组由两名无激素抵抗的兄弟姐妹组成，他们有最严重的骨骼和身体发育迟缓。两例均检测到PDE4D基因缺陷。B组由6例表现出激素抵抗但无低钙血症的患者组成。所有患者均观察到掌骨短小和锥形骨骺。两例检测到PRKAR1A基因缺陷；然而，它们的临床和放射学特征并不相同。面部畸形和发育迟缓较轻，B-3病例检测到PRKAR1A基因缺陷。观察到严重的面部畸形和掌骨畸形，但B-1病例未检测到基因缺陷。C组由7例PHP1a患者组成，其中4例在GNAS基因之一中存在母系遗传的杂合失活突变。C组患者的临床和放射学特征也不相同。
新提出的分类适用于日本患者；然而，B组和C组内仍存在异质性。
