A novel PHOX2B gene mutation in an extremely low birth weight infant with congenital central hypoventilation syndrome and variant Hirschsprung's disease
A novel PHOX2B gene mutation in an extremely low birth weight infant with congenital central hypoventilation syndrome and variant Hirschsprung's disease
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DOI：
10.1016/j.ejmg.2018.09.008
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发表时间：
2019-09-01
影响因子：
1.9
通讯作者：
Hayasaka, Kiyoshi
中科院分区：
文献类型：
--
作者：
Miura, Yuichiro;Watanabe, Tatsuya;Hayasaka, Kiyoshi
先天性中枢性低通气综合征是一种由配对样同源框2B基因突变引起的呼吸控制障碍。配对样同源框2B基因的突变也是先天性巨结肠的原因。变异型先天性巨结肠是一种罕见的疾病，不符合先天性巨结肠的诊断标准，尽管严重的功能性肠梗阻仍然存在。我们报告一例极低出生体重儿合并先天性中枢性肺通气不足症候群及变异型先天性巨结肠症。一名男婴被诊断为胎儿生长受限和羊水过多，由于胎儿状态不安全，在孕龄30周零3天时通过紧急剖宫产分娩。出生体重为979 g，分娩后立即开始重症监护。该患者表现出难治性呼吸暂停，并通过配对样同源框2B基因检测诊断为先天性中枢性通气不足综合征。病人亦表现出顽固性功能性肠梗阻，并通过病理检查，他的肠道标本被诊断为变异型先天性巨结肠症。病人生长缓慢，但肯定与重症监护，包括机械通气和肠外营养。然而，该患者反复患有败血症，并在197天龄时死于真菌血症。这是第一例先天性中枢性肺通气不足综合征合并变异型先天性巨结肠的病例，在该病例中检测到的配对样同源框2B突变（NM_003924. 3：c.441G > C; p.（Gln 147 His））是新的。此病例提示，配对样同源框2B突变不仅导致先天性中枢性肺通气不足综合征和先天性巨结肠，而且还导致人类的变异型先天性巨结肠。它还强调了治疗患有严重和长期功能性肠梗阻的早产儿的极端困难。
Congenital central hypoventilation syndrome is a disorder of respiratory control caused by mutations in the paired-like homeobox 2B gene. Mutations in the paired-like homeobox 2B gene are also responsible for Hirschsprung's disease. Variant Hirschsprung's disease is a rarer disorder that does not meet the diagnostic criteria of Hirschsprung's disease, although severe functional bowel obstruction persists. We present a case of an extremely low birth weight infant with congenital central hypoventilation syndrome and variant Hirschsprung's disease. A male infant who was diagnosed to have fetal growth restriction and polyhydramnios was delivered by emergency cesarean section at 30 weeks and 3 days of gestational age due to non-reassuring fetal status. The birth weight was 979 g, and intensive care was started immediately following delivery. The patient exhibited refractory apnea and was diagnosed with congenital central hypoventilation syndrome by genetic testing of the paired-like homeobox 2B gene. The patient also exhibited refractory functional bowel obstruction and was diagnosed to have variant Hirschsprung's disease through pathological examination of his intestinal specimens. The patient grew slowly but surely with intensive care including mechanical ventilation and parenteral nutrition. However, the patient repeatedly suffered from sepsis and died of fungemia at 197 days of age. This is the first congenital central hypoventilation syndrome case that was accompanied with variant Hirschsprung's disease, and the paired-like homeobox 2B mutation detected in this case (NM_003924.3: c.441G > C; p. (Gln147His)) is novel. This case suggests that the paired-like homeobox 2B mutation causes not only congenital central hypoventilation syndrome and Hirschsprung's disease, but also variant Hirschsprung's disease in humans. It also highlights the extreme difficulty in treating premature infants with severe and prolonged functional bowel obstruction.