目的 MTM1基因变异所致X连锁肌管型肌病（XLMTM）是一种罕见神经肌肉病，目前对我国XLMTM患者早期自然史和诊断性临床特征的系统性总结尚不完善。方法 回顾性收集2018年1月至2024年8月在两家医院新生儿重症监护室住院并经基因确诊的严重型XLMTM患儿的临床资料，包括围产期表现、新生儿期表型、基因检测结果及转归，并系统总结该病的生命早期自然史。结果 共收集6例确诊患儿，均为男性，平均胎龄为（37.5±2.6）周；3例孕期超声提示羊水过多，1例孕24周发现母亲球拍状胎盘，2例有同家系多例男婴早期死亡家族史。所有患儿均在出生后即出现新生儿窒息，Apgar评分1分钟3~6分，5分钟4~7分。所有患儿出生后均表现为严重新生儿呼吸衰竭和特征性全身松软/重度肌张力低下，需全程机械通气、营养支持、鼻饲喂养。所有患儿均存在继发孔型房间隔缺损（ASDⅡ型），缺损直径2.0~4.5 mm。伴随畸形包括隐睾、小下颌及四肢细长。所有患儿均在6个月内死亡，中位生存时间32（3~150）天。死亡原因主要包括呼吸衰竭、感染及放弃治疗。基因分析显示5例MTM1基因变异为母系遗传，1例为新发变异。5例变异位于Rac1诱导的招募结构域，1例位于蛋白酪氨酸磷酸酶催化位置。结论 严重型XLMTM新生儿临床表型高度一致，其自然史核心特征包括新生儿窒息、严重呼吸衰竭、特征性重度肌张力低下，以及特殊面容、四肢畸形等诊断指向性信息。本队列提示，我国XLMTM新生儿自然史可能与国际报道存在差异，不同类型MTM1基因变异均可导致极重表型。多数患儿在围产期即有羊水过多等早期预警指标，出生后病情进展迅速，预后差，应强调对高危孕妇及其胎儿开展早期遗传学筛查与诊断的重要性。

Objective X-linked myotubular myopathy (XLMTM) caused by MTM1 gene variation is a rare neuromuscular disease. Currently, the systematic summary of the early natural history and diagnostic clinical characteristics of XLMTM patients in China is still incomplete. Methods We retrospectively reviewed clinical data, including perinatal findings, neonatal phenotype, genetic results, and outcomes, of male neonates with genetically confirmed severe XLMTM who were admitted to the neonatal intensive care units (NICUs) in two hospitals, between January 2018 and August 2024. And the early life natural history of this disease was systematically summarized. Results Six male patients were included in this cohort. The average gestational age was (37.5±2.6) weeks. Three cases were indicated with polyhydramnios by prenatal ultrasonography, one case was found with a racquet-shaped placenta at 24 weeks of gestation, and two cases had a family history of multiple early deaths among male infants within the same lineage. Neonatal asphyxia occurred immediately after birth in 6 children, with Apgar scores ranging from 3 to 6 at 1 minute and 4 to 7 at 5 minutes. All the patients presented with severe neonatal respiratory failure and characteristic profound hypotonia/floppy, and required continuous mechanical ventilation, nutritional support and nasogastric feeding throughout the course. All the patients had secondary hole-type atrial septal defect (ASD type II), with defect diameters ranging from 2.0 to 4.5 mm. Associated findings included cryptorchidism, micrognathia and slender limbs. All patients died within 6 months, with a median survival of 32 (3-150) days. The leading causes of death included respiratory failure, infection, and withdrawal of care. Genetic analysis revealed five maternally inherited variants and one de novo mutation in the MTM1 gene; five variants were located in the Rac1-induced recruitment domain (RID), and one in the protein tyrosine phosphatase (PTP) catalytic domain. Conclusions Severe XLMTM neonates exhibit a highly uniform clinical phenotype. The core features of its natural history, including neonatal asphyxia, respiratory failure, characteristic profound hypotonia, specific dysmorphic features and limb anomalies, serve as key diagnostic pointers. This cohort suggests that the natural history of XLMTM neonates in China may differ from international reports, and different types of MTM1 gene variations can all lead to extremely severe phenotypes. Given that most patients show early warning signs such as polyhydramnios during the perinatal period, and the disease progresses rapidly with an extremely poor prognosis, the importance of early genetic screening and diagnosis for high-risk pregnant women and their fetuses is underscored.