1/6. Maternal uniparental disomy for chromosome 14 in a boy with a normal karyotype.We report on a boy with a maternal uniparental disomy for chromosome 14 (UPD(14)). At 7 years of age he was referred to us by the paediatrician because of symptoms of prader-willi syndrome (PWS). He showed short stature, obesity, mild developmental delay, cryptorchidism, and some mild dysmorphic features. The history further indicated intrauterine growth retardation at the end of the pregnancy. His mother was 44 years of age at the time of his birth. After birth he showed hypotonia with poor sucking, for which gavage feeding was needed. Motor development was delayed. After 1 year he became obese despite a normal appetite. Recurrent middle ear infections, a high pain threshold, and a great skill with jigsaw puzzles were reported. There were no behavioural problems or sleep disturbance. Chromosomal analysis was normal (46,XY). dna analysis for prader-willi syndrome showed no abnormalities. Two years later he was re-examined because we thought his features fitted the PWS-like phenotype associated with maternal UPD(14). At that time precocious puberty was evident. dna analysis showed maternal heterodisomy for chromosome 14. In all the previously described 11 cases with maternal UPD(14), a Robertsonian translocation involving chromosome 14 was detected cytogenetically before dna analysis. This is the first report of diagnosis of maternal UPD(14) based on clinical features. This finding underlines the importance of dna analysis for maternal UPD(14) in patients with a similar PWS-like phenotype even without previous identification of a Robertsonian translocation involving chromosome 14.- - - - - - - - - - ranking = 1keywords = pregnancy (Clic here for more details about this article) |
2/6. A fetus with prader-willi syndrome showing normal diurnal rhythm and abnormal ultradian rhythm on heart rate monitoring.Clinical features of prader-willi syndrome in neonates are marked hypotonia with the absence of crying and feeding difficulty so that prenatal diagnosis of prader-willi syndrome is strongly hoped in order to provide appropriate medical and psychological care for neonates and their families. However, the clinical picture of prader-willi syndrome in utero has not been well described. We report a pregnancy associated with prader-willi syndrome manifesting polyhydramnios, large biparietal diameter of the fetus and characteristic fetal heart rate pattern: prolonged inactive periods and diurnal variation of the incidence of heart rate accelerations. These findings may offer a clue to the prenatal diagnosis of prader-willi syndrome, although molecular cytogenetics is mandatory for the definite diagnosis.- - - - - - - - - - ranking = 1keywords = pregnancy (Clic here for more details about this article) |
3/6. Double supernumerary isodicentric chromosomes derived from 15 resulting in partial hexasomy.We report two unrelated patients each with two supernumerary marker chromosomes (SMCs) derived from chromosome 15, and thus resulting in partial hexasomy. Hexasomy in the one case (family 1) was diagnosed at prenatal diagnosis and did not include the Prader-Willi/Angelman critical region (PWACR). The double SMCs were also found in the mother, the pregnancy continued to term, and an apparently phenotypically normal child was born. This represents the first report of transmission of double SMCs from mother to child. In the second case (family 2), the hexasomy did include the PWACR and was de novo in origin. This patient manifested severe psychomotor retardation, clefting of the soft palate, hypotonia, seizure-like episodes, and other phenotypic features. The aberrant phenotype is attributable to the hexasomy for the PWACR gene loci. The normal homologs of chromosome 15 proved to be biparental in origin while the two SMCs appeared maternal.- - - - - - - - - - ranking = 1keywords = pregnancy (Clic here for more details about this article) |
4/6. Obstetric aspects of the prader-willi syndrome.The prader-willi syndrome (PWS) is a complex, multisystem disorder. The syndrome affects the central nervous system, with a predilection for the hypothalamus. The clinical picture in PWS is very variable, and depends on the age of the affected child. Frequently, the most prominent features such as obesity, mental retardation and behavioral disorders do not become evident until the later childhood stage, which can lead to underdiagnosis or late diagnosis in early childhood. Because of the long-term implications of this syndrome, it is important to recognize its features as soon as possible so that early counseling of parents and the affected child is possible. Because PWS can also lead to complications in both pregnancy and labor, proper diagnosis in the fetus can also help optimize perinatal care in affected children. In three cases we illustrate that certain combinations of obstetric symptoms such as polyhydramnios, diminished fetal movements, malpresentation and abnormal fetal heart rhythm can help alert clinicians to the possibility of this syndrome in fetuses.- - - - - - - - - - ranking = 1keywords = pregnancy (Clic here for more details about this article) |
5/6. death during GH therapy in children with prader-willi syndrome: description of two new cases.A few cases of death worldwide during GH treatment in pediatric patients with prader-willi syndrome (PWS) have been recently described. The evaluation of further cases is needed to better identify possible causal mechanism(s), as well as to suggest some additional guidelines for prevention. We report the death of 2 additional children with genetically confirmed PWS in the first months of GH therapy. Case 1: This 3.9-yr-old girl was born at 39 weeks gestation. Low GH response to two stimulation tests was observed. GH administration was started at the age of 3.5 yr (0.33 mg/kg per week), when the patient was at 130% of her ideal body weight (ibw). hypertrophy of adenoids was previously demonstrated. snoring and sleep apnea were present before GH treatment, and did not increase during therapy. Four months later she died at home suddenly in the morning. Case 2: This patient was a 6.3-yr-old boy. He was born at term after an uneventful pregnancy. At the age of 6 yr, his weight was at 144% of his ibw. He showed reduced GH secretion during provocation tests, and GH therapy was started (0.20 mg/kg per week). The previously reported nocturnal respiratory impairment had worsened after beginning GH administration. Tonsils and adenoids hypertrophy were noted. At the age of 6.3 yr he died at home in the morning following an acute crisis of apnea. These additional cases seem to confirm that some children with PWS may be at risk of sudden death at the beginning of GH therapy.- - - - - - - - - - ranking = 1keywords = pregnancy (Clic here for more details about this article) |
6/6. prenatal diagnosis of uniparental disomy 15 following trisomy 15 mosaicism.Maternal uniparental disomy 15 (UPD15), responsible for approximately 25 per cent of prader-willi syndrome cases, is usually caused by maternal meiosis I non-disjunction associated with advanced maternal age. These cases may initially be detected as mosaic trisomy 15 during routine prenatal diagnostic studies. In such cases, PCR (polymerase chain reaction) microsatellite analysis of uncultured cells makes prospective prenatal diagnosis for UPD15 possible with results available in 2-4 days. We have performed molecular analyses on a series of seven cases of mosaic trisomy 15 identified in amniotic fluid (AF, n = 3) or chorionic villus samples (CVS, n = 4) from patients initially referred for advanced maternal age or abnormal triple screen. In all cases, the maternal ages were > or = 35 years and maternal meiosis I non-disjunction was documented as the cause of the trisomy in all informative cases (n = 5). Of the three case with mosaic trisomy 15 at amniocentesis, two showed the presence of the trisomy in the fetus. Molecular analysis showed one case with maternal UPD15 in the euploid cell line and one case with biparental inheritance. Both of these families elected to terminate the pregnancies based on the presence of true fetal mosaicism. In the third case, low-level trisomy 15 mosaicism in the amniotic fluid was not confirmed in a follow-up amniotic fluid sample and molecular analysis indicated biparental inheritance in the fetus. For the four trisomy 15 mosaics detected at CVS, molecular analysis was performed on direct amniotic fluid cell lysates for prospective diagnosis of UPD at 14-16 weeks' gestation. Follow-up cytogenetic analysis of the amniotic fluid in all four cases was normal, indicating confined placental mosaicism. Molecular analysis showed one of these four cases to have maternal heterodisomy 15. Based on the likelihood of prader-willi syndrome due to maternal UPD15, the couple chose to terminate the pregnancy. The total of two of seven cases of trisomy 15 mosaicism resulting in UPD15 is consistent with the theoretical expectation of one-third and indicates a high risk of UPD in such pregnancies. Therefore, UPD testing should be offered in all cases of mosaic trisomy 15 encountered in CVS or amniocentesis.- - - - - - - - - - ranking = 1keywords = pregnancy (Clic here for more details about this article) |