ABSTRACT
Monozygotic twins were previously regarded as "identical". By now an increasing number of case reports of monozygotic but discordant twins have been reported, and therefore discordance between monozygotic twins is being investigated intensively. We report a case of female preterm monozygotic twins who were discordant for fetal megacystis due to cloacal dysgenesis. Pregnancy was achieved after intracytoplasmatic sperm injection and transfer of 2 embryos. By the first trimester fetal megacystis with consecutive oligohydramnios and hypoplasia of the lungs was diagnosed. Both foetuses had normal karyotypes. After delivery at 25+3 weeks of gestation due to premature labour, the affected child was treated palliatively and died within 2 hours. In the postmortem physical examination, a cloacal dysgenesis was detected. In the male foetus, megacystis is typically caused by obstructive uropathy. In the rarely affected female foetus, it usually results from complex urogenital malformations like cloacal dysgenesis which originates from disruption during gastrulation. We identified 10 case series of mono- or dizygotic twins who were discordant either for fetal megacystis or for cloacal dysgenesis. Issues like conception, zygosity, sex, karyotype and aetiology of fetal megacystis were not reported in all cases. Discordance between monozygotic twins for structural birth defects is closely linked to the twinning process itself. Assisted reproduction is said to generate a higher rate of monozygotic twin pregnancies and to be responsible for a higher prevalence of chromosomal aberrations or congenital malformations. With regard to conception, zygosity, sex, karyotype and combination of malformations, our case is unique.
Subject(s)
Cloaca/abnormalities , Cloaca/diagnostic imaging , Duodenum/abnormalities , Fetal Diseases/diagnostic imaging , Infertility, Female/therapy , Sperm Injections, Intracytoplasmic , Twins, Monozygotic , Ultrasonography, Prenatal/methods , Urinary Bladder/abnormalities , Abnormalities, Multiple/diagnostic imaging , Abnormalities, Multiple/genetics , Adult , Diagnosis, Differential , Duodenum/diagnostic imaging , Female , Fetal Diseases/etiology , Humans , Infant, Premature , Pregnancy , Urinary Bladder/diagnostic imagingABSTRACT
Hypermethylation of CpG island promoters is associated with transcriptional inactivation of tumor suppressor genes in neoplasia. Inactivation of p16 and Pten was related to the development of pheochromocytomas. In this report, we investigated the methylation status of the p16INK4a cell cycle inhibitor gene and other prominent tumor-related genes ( PTEN, RASSF1 A, CDH1, MSH2, MLH1, VHL, and TIMP3) in sporadic and multiple endocrine neoplasia type 2 (MEN2) pheochromocytomas by methylation-specific PCR. Hypermethylation was detected in 48 % of pheochromocytomas for RASSF1 A, 24 % for p16, 36 % for MSH2, 16 % for CDH1, and 8 % for PTEN. No VHL, MLH1, and TIMP3 methylation was observed. Interestingly, the frequency of p16 inactivation in familial tumors was higher (5 out of 12, 42 %) than in sporadic tumors (1 out of 13, 8 %; p = 0.047) and RASSF1 A inactivation was more common in the hereditary tumors (58 %) compared to the sporadic tumors (38 %). Combined methylation of RASSF1 A and p16 was found only in MEN2-related pheochromocytomas. Thus, a subset of hereditary pheochromocytomas displays preferential methylation of p16 and RASSF1 A.
