Prenatal Identification and Molecular Characterization of Two Simultaneous De Novo Interstitial Duplications of Chromosomal Regions 7p22.1p21.1 and 15q24.1.

The occurrence of simultaneous de novo chromosomal aberrations is extremely rare. Here, we describe two, previously unreported, simultaneous de novo interstitial duplications of chromosomes 7p and 15q. Amniocentesis was completed for a healthy gravida 4 para 3 woman due to her advanced maternal age and concurrent ultrasound findings of partial vermian agenesis, choroid-plexus cysts, and hypoplastic nasal bone. Cytogenetic analysis of cultured amniocytes by conventional chromosome analysis, comparative genomic hybridization, and fluorescence in situ hybridization revealed two interstitial duplications of the chromosomal regions 7p22.1p21.1 and 15q24.1, leading to partial trisomy of 7p and 15q and karyotype 46,XY,dup(7)(p22.1-p21.1),dup (15)(q24.1). Parental chromosomal analysis did not identify any heritable changes, suggesting both mutations were de novo in nature. Postnatal examination of the neonate was significant for low set ears, thick helices, flat nasal bridge, ankyloglossia, and aberrant head shape and size concerning for craniosynostosis. Postnatal MRI was consistent with Dandy-Walker variant showing hypogenesis of the inferior cerebellar vermis. To our knowledge, there are no prenatal or postnatal reports of comparable duplications involving these two regions simultaneously. Continued observation of the neonate may reveal further phenotypic consequences of these two simultaneous de novo interstitial duplications.

Mosaic trisomy 13: understanding origin using SNP array.

BACKGROUND: Trisomy 13 occurs in 1/10,000-20,000 live births, and mosaicism accounts for 5% of these cases. Phenotype and outcome of mosaic trisomy 13 are variable and poorly understood. Microsatellite analyses of trisomy 13 have indicated the high incidence of maternal meiotic origin and reduced recombination, but no study has focused on mosaic trisomy 13 in live born patients. METHODS AND RESULTS: Single-nucleotide polymorphism (SNP) array, fluorescence in situ hybridisation and bioinformatics analyses were performed in three cases of mosaic trisomy 13. Two cases of complete mosaic trisomy 13 originated from meiosis I non-disjunction followed by trisomic rescue; one had crossovers resulting in segmental uniparental disomy in the disomic line, and one had no crossover. Mosaicism for partial trisomy 13 in the third complex case either arose from meiosis II non-disjunction without crossover or in early mitosis followed by anaphase lags. The extra chromosome 13 was maternal in origin in all three cases. Mosaicism percentage calculated from B allele frequencies ranged from 30 to 50. CONCLUSIONS: Genotypes and copy number information provided by SNP array allow determination of parental origin and uniparental disomy status and direct quantification of mosaicism. Such information may lead to a better understanding of mechanisms underlying mosaic aneuploidies and the observed phenotypic variability and better prediction of recurrent risk.

Successful pregnancy outcome in Ehlers-Danlos syndrome, vascular type.

BACKGROUND: Ehlers-Danlos syndrome (EDS) is a rare connective tissue disorder characterized by tissue fragility, translucent skin and joint hypermobility. Patients with the vascular type of EDS are prone to spontaneous arterial and visceral rupture. Pregnancy for women with vascular EDS can be life-threatening. Mortality rates are high due to the increased risk for uterine and arterial rupture in the peripartum period. CASE: We describe the counseling, multidisciplinary management, protocol, and successful pregnancy outcome of a 32-year-old woman with vascular EDS. CONCLUSION: There is no consensus in the literature on the timing and mode of delivery for pregnant women with vascular EDS. The management undertaken in our patient may assist others in optimizing the perinatal outcome in other women who elect to continue their pregnancy despite the risks of this severe medical condition.