Fryns Syndrome Associated with Recessive Mutations in PIGN in two Separate Families.

Fryns syndrome is an autosomal recessive condition characterized by congenital diaphragmatic hernia (CDH), dysmorphic facial features, distal digital hypoplasia, and other associated malformations, and is the most common syndromic form of CDH. No gene has been associated with this condition. Whole-exome sequence data from two siblings and three unrelated individuals with Fryns syndrome were filtered for rare, good quality, coding mutations fitting a recessive inheritance model. Compound heterozygous mutations in PIGN were identified in the siblings, with appropriate parental segregation: a novel STOP mutation (c.1966C>T: p.Glu656X) and a rare (minor allele frequency <0.001) donor splice site mutation (c.1674+1G>C) causing skipping of exon 18 and utilization of a cryptic acceptor site in exon 19. A further novel homozygous STOP mutation in PIGN (c.694A>T: p.Lys232X) was detected in one unrelated case. All three variants affected highly conserved bases. The two remaining cases were negative for PIGN mutations. Mutations in PIGN have been reported in cases with multiple congenital anomalies, including one case with syndromic CDH. Fryns syndrome can be caused by recessive mutations in PIGN. Whether PIGN affects other syndromic and non-syndromic forms of CDH warrants investigation.

Uptake of invasive prenatal tests in pregnancies conceived via assisted reproductive technologies: the experience in Queensland, Australia.

OBJECTIVE: Prenatal diagnosis of a chromosomal abnormality currently involves the use of an invasive procedure, which has a risk of fetal loss. The aim of this study was to identify whether pregnancies conceived via assisted reproductive technologies were more or less likely to be subjected to an invasive procedure compared with pregnancies that were conceived spontaneously. METHOD: Population data were collated from three private ultrasound clinics across southeast Queensland, Australia. RESULTS: Of the 15,032 spontaneously conceived pregnancies, 775 (5.2%) had invasive testing, while 95 (6.0%) of the 1581 pregnancies conceived through assisted reproductive technologies had invasive testing. When the uptake of testing is adjusted by the maternal age the assisted reproductive population was significantly less likely to pursue invasive testing (p = 0.003). Similarly when adjusted for the combined first trimester screen risk estimate, the assisted reproduction population is significantly less likely to undergo invasive testing than the spontaneous population (p = 0.005). CONCLUSION: Pregnancies conceived using assisted reproductive technologies are significantly less likely to be subjected to invasive testing than pregnancies conceived spontaneously in women of the same age and combined first trimester screen risk.

A case of Beare-Stevenson syndrome with a broad spectrum of features and a review of the FGFR2 Y375C mutation phenotype.

We present a case of Beare-Stevenson syndrome with a broad range of phenotypic features including craniosynostosis, cutis gyrata, choanal stenosis, bifid scrotum with perineal hypospadias and a caudal appendage. The paternal age at the time of conception was 62 years consistent with a paternal age effect. Mutation analysis was undertaken and demonstrated the FGFR2 Y375C mutation. This case, one of only nine with molecular analysis, confirms the significant morbidity associated with this syndrome.

Recurrence of Mowat-Wilson syndrome in siblings with the same proven mutation.

Mowat-Wilson syndrome (MWS) is a mental retardation syndrome associated with distinctive facial features, microcephaly, epilepsy, and a variable spectrum of congenital anomalies, including Hirschsprung disease (HSCR), agenesis of the corpus callosum, genitourinary abnormalities, and congenital heart disease. Heterozygous mutations or deletions involving the gene ZFHX1B (previously SIP1) [OMIM 605802] have recently been found to cause MWS. There have previously been no reports of a sibling recurrence of this syndrome. A brother and sister are described with clinical features of MWS, where both have the same truncating mutation in exon 8 of ZFHX1B. As their parents are phenotypically normal and do not have the mutation in lymphocyte-derived DNA, the most likely explanation is germ-line mosaicism.

Craniopagus: second Brisbane case. Case report.

Craniopagus is a rare and intriguing condition with an incidence of one in 2.5 million births. The chance of a neurosurgeon seeing a case in a working lifetime is unlikely. The chances of two cases from the same community within 12 months are remote in the extreme. The authors present a second case of craniopagus born and separated in Brisbane, Australia, in 2001 and discuss the intricacies of surgical separation and the lessons learned.

Separation of craniopagus joined at the occiput. Case report.

Siamese or conjoined twins have intrigued both the physician and layperson for centuries. The craniopagus type (joined at the head) is exceedingly rare, with an incidence of one in 2.5 million births. Most clinicians never see a case of craniopagus, and those who do rarely see more than one. The authors present a case of the craniopagus type of conjoined twins born and recently separated in Brisbane, Australia. The prenatal diagnosis, subsequent investigations, separation, and outcome are presented.