Shinawi Marwan, Boileau Catherine, Brik Riva, Mandel Hanna, Bentur Lea
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Pediatr Pulmonol. 2005 Apr;39(4):374-8. doi: 10.1002/ppul.20174.
Neonatal Marfan syndrome is an autosomal-dominant connective tissue disease with unique clinical manifestations and mutations. We describe the clinical course of an infant with neonatal Marfan syndrome that had the novel IVS31-2A > G splice site mutation in fibrillin-1. This mutation affects the second base of the acceptor consensus splice site of intron 31, and probably leads to abnormal splicing events. The patient presented with respiratory distress and heart murmur in early neonatal life. Cardiac evaluation revealed pulmonic stenosis, atrioventricular regurgitation, and a dilated aortic root that were controlled by balloon dilatation of the pulmonic stenosis and medications for congestive heart failure. At age 3 months, he presented with severe respiratory distress caused by upper and lower airway obstruction. Imaging studies showed severe pulmonary emphysema, and a bronchoscopy demonstrated megatracheobronchomalacia, an unusual finding in this syndrome. Subsequently, the patient developed recurrent hyperinflation of the right and left lungs, with emphysematous changes and mediastinal shift. After discussing with his parents the grave prognosis for neonatal Marfan syndrome, he was discharged home with oxygen treatment and died at home at age 4.5 months. This case report demonstrates and discusses pulmonary involvement in neonatal Marfan syndrome and the difficult therapeutic challenges created by the severe cardiopulmonary abnormalities in this invariably fatal condition.
新生儿马方综合征是一种常染色体显性遗传性结缔组织疾病，具有独特的临床表现和突变类型。我们描述了一名患有新生儿马方综合征的婴儿的临床病程，该婴儿在原纤维蛋白-1中存在新的IVS31-2A > G剪接位点突变。此突变影响内含子31受体一致性剪接位点的第二个碱基，可能导致异常剪接事件。该患者在新生儿早期出现呼吸窘迫和心脏杂音。心脏评估显示存在肺动脉狭窄、房室反流以及主动脉根部扩张，通过肺动脉狭窄球囊扩张术和治疗充血性心力衰竭的药物对病情进行了控制。3个月大时，他因上、下气道阻塞出现严重呼吸窘迫。影像学检查显示严重肺气肿，支气管镜检查显示气管支气管巨大软化，这在该综合征中是不常见的发现。随后，患者出现左右肺反复过度充气，伴有肺气肿改变和纵隔移位。在与患儿父母讨论了新生儿马方综合征的严重预后后，他在接受氧疗的情况下出院，并于4.5个月时在家中死亡。本病例报告展示并讨论了新生儿马方综合征的肺部受累情况，以及这种总是致命的疾病中严重心肺异常所带来的艰难治疗挑战。
