Zeng Chunhua, Lin Yunting, Lu Zhikun, Chen Zhen, Jiang Xiaoling, Mao Xiaojian, Liu Zongcai, Lu Xinshuo, Zhang Kangdi, Yu Qiaoli, Wang Xiaoya, Huang Yonglan, Liu Li
Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Rd, Guangzhou, 510623, China.
Department of Radiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Rd, Guangzhou, 510623, China.
BMC Musculoskelet Disord. 2020 Mar 6;21(1):154. doi: 10.1186/s12891-020-3181-0.
Hajdu-Cheney syndrome (HCS) is a rare inherited skeletal disorder caused by pathogenic mutations in exon 34 of NOTCH2. Its highly variable phenotypes make early diagnosis challenging. In this paper, we report a case of early-onset HCS with severe phenotypic manifestations but delayed diagnosis.
The patient was born to non-consanguineous, healthy parents of Chinese origin. She presented facial anomalies, micrognathia and skull malformations at birth, and was found hearing impairment, congenital heart disease and developmental delay during her first year of life. Her first visit to our center was at 1 year of age due to cardiovascular repair surgery for patent ductus arteriosus (PDA) and ventricular septal defect (VSD). Skull X-ray showed wormian bones. She returned at 7 years old after she developed progressive skeletal anomalies with fractures. She presented with multiple wormian bones, acro-osteolysis, severe osteoporosis, bowed fibulae and a renal cyst. Positive genetic test of a de novo heterozygous frameshift mutation in exon 34 of NOTCH2 (c.6426dupT) supported the clinical diagnosis of HCS.
This is the second reported HCS case caused by the mutation c.6426dupT in NOTCH2, but presenting much earlier and severer clinical expression. Physicians should be aware of variable phenotypes so that early diagnosis and management may be achieved.
哈伊杜-切尼综合征（HCS）是一种罕见的遗传性骨骼疾病，由NOTCH2基因第34外显子的致病性突变引起。其高度可变的表型使得早期诊断具有挑战性。在本文中，我们报告了一例早发性HCS病例，该病例临床表现严重但诊断延迟。
患者出生于非近亲结婚、健康的华裔父母。她出生时即出现面部异常、小颌畸形和颅骨畸形，在出生后第一年被发现有听力障碍、先天性心脏病和发育迟缓。由于动脉导管未闭（PDA）和室间隔缺损（VSD）的心血管修复手术，她在1岁时首次就诊于我们中心。颅骨X线显示有缝间骨。在出现进行性骨骼异常并伴有骨折后，她于7岁时再次就诊。她表现为多处缝间骨、肢端骨质溶解、严重骨质疏松、腓骨弯曲和一个肾囊肿。NOTCH2基因第34外显子的一个新发杂合移码突变（c.6426dupT）的基因检测阳性，支持了HCS的临床诊断。
这是第二例报道的由NOTCH2基因c.6426dupT突变引起的HCS病例，但临床表现出现得更早且更严重。医生应了解其可变的表型，以便实现早期诊断和管理。
