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. © 2005 Wiley‐Liss, Inc.

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.

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.

BACKGROUND AND PURPOSE: Ganglionic eminence abnormalities on fetal MR imaging are associated with cerebral malformations. Their presumed genetic basis and associated postnatal outcomes remain largely unknown. We aimed to elucidate these through a multicenter study. MATERIALS AND METHODS:Between January 2010 and June 2020, seven hospitals in 2 countries performing fetal MR imaging examinations identified fetal MR imaging studies demonstrating ganglionic eminence enlargement, cavitation, or both. Cases with no genetic diagnosis, no whole exome sequencing, or no outcome of a liveborn child were excluded. Head size was classified as large (fronto-occipital diameter . 95th centile), small (fronto-occipital diameter ,5th centile), or normal.RESULTS: Twenty-two fetuses with ganglionic eminence abnormalities were identified. Of 8 with large heads, 2 were diagnosed with MTOR mutations; 1 with PIK3CA mutation-producing megalencephaly, polymicrogyria, polydactyly, hydrocephalus (MPPH) syndrome; 3 with TSC mutations; 1 with megalencephaly capillary malformation syndrome; and 1 with hemimegalencephaly. Cardiac rhabdomyoma was present prenatally in all cases of TSC; mutation postaxial polydactyly accompanied megalencephaly capillary malformation and MPPH. Of 12 fetuses with small heads, 7 had TUBA1A mutations, 1 had a TUBB3 mutation, 2 had cobblestone lissencephaly postnatally with no genetic diagnosis, 1 had a PDHA1 mutation, and 1 had a fetal akinesia dyskinesia sequence with no pathogenic mutation on trio whole exome sequencing. One of the fetuses with a normal head size had an OPHN1 mutation with postnatal febrile seizures, and the other had peri-Sylvian polymicrogyria, seizures, and severe developmental delay but no explanatory mutation on whole exome sequencing.CONCLUSIONS: Fetal head size and extracranial prenatal sonographic findings can refine the phenotype and facilitate genetic diagnosis when ganglionic eminence abnormality is diagnosed with MR imaging.

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.