Barisic N, Müller J S, Paucic-Kirincic E, Gazdik M, Lah-Tomulic K, Pertl A, Sertic J, Zurak N, Lochmüller H, Abicht A
Department of Pediatrics, University Medical School, Zagreb, Croatia.
Eur J Paediatr Neurol. 2005;9(1):7-12. doi: 10.1016/j.ejpn.2004.10.008. Epub 2004 Dec 13.
Congenital myasthenic syndromes (CMS) result from mutations in various synapse-associated genes. Mutations in the choline acetyltransferase (CHAT) gene cause a presynaptic CMS associated with episodic apnea (CMS-EA). We present two unrelated Croatian children affected by CMS-EA. Beside other clinical findings characteristic for CMS, both patients manifested intermittent apneas since early infancy. Whereas the course of disease is mild in the female patient (patient 2), the male patient (patient 1) experienced recurrent and severe episodes of apnea despite adequate treatment with AChE-inhibitors and shows a global developmental delay with delayed myelination and signs of hypoxic-ischemic injury in brain imaging. Interestingly, sequencing of the CHAT gene revealed identical, compound heterozygous mutations S694C and T354M in both children. These findings are in line with a remarkable clinical heterogeneity observed in patients with CHAT mutations and emphasize the potential role of apneic crises for the development of secondary hypoxic brain damage and psychomotor retardation.
先天性肌无力综合征（CMS）由各种与突触相关的基因突变引起。胆碱乙酰转移酶（CHAT）基因突变会导致与发作性呼吸暂停相关的突触前CMS（CMS-EA）。我们报告了两名患CMS-EA的克罗地亚非亲缘儿童。除了CMS的其他典型临床特征外，两名患者自婴儿早期就表现出间歇性呼吸暂停。女性患者（患者2）的病程较轻，而男性患者（患者1）尽管接受了乙酰胆碱酯酶抑制剂的充分治疗，仍经历了反复且严重的呼吸暂停发作，并表现出全面发育迟缓，伴有髓鞘形成延迟以及脑成像显示的缺氧缺血性损伤迹象。有趣的是，CHAT基因测序显示两名儿童均存在相同的复合杂合突变S694C和T354M。这些发现与CHAT基因突变患者中观察到的显著临床异质性一致，并强调了呼吸暂停危象在继发性缺氧性脑损伤和精神运动发育迟缓发生中的潜在作用。
