Exome sequencing in a family with an X-linked lethal malformation syndrome: clinical consequences of hemizygous truncating OFD1 mutations in male patients.

Oral-facial-digital syndrome type 1 (OFD1; OMIM #311200) is an X-linked dominant disorder, caused by heterozygous mutations in the OFD1 gene and characterized by facial anomalies, abnormalities in oral tissues, digits, brain, and kidney; and male lethality in the first or second trimester pregnancy. We encountered a family with three affected male neonates having an 'unclassified' X-linked lethal congenital malformation syndrome. Exome sequencing of entire transcripts of the whole X chromosome has identified a novel splicing mutation (c.2388+1G > C) in intron 17 of OFD1, resulting in a premature stop codon at amino acid position 796. The affected males manifested severe multisystem complications in addition to the cardinal features of OFD1 and the carrier female showed only subtle features of OFD1. The present patients and the previously reported male patients from four families (clinical OFD1; Simpson-Golabi-Behmel syndrome, type 2 with an OFD1 mutation; Joubert syndrome-10 with OFD1 mutations) would belong to a single syndrome spectrum caused by truncating OFD1 mutations, presenting with craniofacial features (macrocephaly, depressed or broad nasal bridge, and lip abnormalities), postaxial polydactyly, respiratory insufficiency with recurrent respiratory tract infections in survivors, severe mental or developmental retardation, and brain malformations (hypoplasia or agenesis of corpus callosum and/or cerebellar vermis and posterior fossa abnormalities).

[Double outlet right ventricle and pulmonary atresia with a birth weight of 1092 g].

A premature infant with double outlet right ventricle and pulmonary atresia with a birth weight of 1092 g is reported. He underwent right modified Blalock-Taussig (RMBT) shunt with an expand-polytetrafluoroethylene (ePTFE) tube of 3.0 mm in diameter between the right subclavian artery and the right pulmonary artery through right thoracotomy. Eleven days later, he had to undergo central shunt between the innominate artery and the main pulmonary trunk due to poor pulmonary blood flow. Soon after the central shunt, severe heart failure occurred due to excessive pulmonary blood flow. RMBT division was performed immediately. He finally attained definitive repair at 17 months of age. Postoperative course was uneventful and he was discharged on the 17th postoperative day.