Eleftheria Papadopoulou

A report of pure 7p duplication syndrome and review of the literature

We report on a case of a 9‐month‐old female infant with a direct duplication of the 7p13‐p22.1 chromosome region diagnosed by combining conventional cytogenetic, FISH, and multicolor banding (MCB) studies. Traditional G‐banding detected a partial 7p duplication, which was further demonstrated to be entirely of chromosome 7 origin by using a whole chromosome paint for chromosome 7, and derived from 7p13‐p22.1 by MCB. The infant presented with characteristic dysmorphic features, psychomotor retardation, and generalized hypotonia. The phenotypic manifestations of partial 7p trisomy with or without other chromosome involvement are briefly reviewed. Our observations in combination with other cases confirm that 7p trisomy due to dir dup(7p) can be regarded as a defined chromosome syndrome.

CERVICAL LYMPHADENOPATHY IN CHILDHOOD EPIDEMIOLOGY AND MANAGEMENT

Cervical lymphadenopathy (CL) is common in childhood. The aim of this study is to evaluate the etiology, follow-up, and treatment of persistent CL. The authors studied retrospectively 50 children with CL, hospitalized at the Department of Pediatrics and Pediatrics Surgery. Patients underwent ultrasonography. Thirty-six percent presented abnormal ultrasonographic image and underwent excisional biopsy. Biopsies revealed 4 thyroglossal cysts, 3 branchial cysts, 1 hemangioma, 2 sebaceous cysts, 1 dermoid cyst, 5 occurrences of tuberculosis lymphadenitis, 1 occurrence of Bartonella henselae lymphadenopathy, and 1 case of non-Hodgkin lymphoma. In conclusion, CL is usually a benign finding; bacterial and viral infections are the most common causes. Ultrasonography help in etiology and follow-up of CL.

CNS imaging is a key diagnostic tool in the evaluation of patients with CFC syndrome: Two cases and literature review†

Cardio‐facio‐cutaneous (CFC) syndrome is characterized by a variable degree of cognitive impairment, and multiple congenital anomalies including characteristic facies, cardiac, and ectodermal abnormalities. CFC syndrome is caused by mutations in the genes BRAF, MEK1, or MEK2. Here we provide a follow‐up report on two patients presenting distinct facial appearance and other features of the syndrome, and we present the first molecular evidence of paternal origin for a CFC‐causing germline mutation. Brain imaging revealed a lipoma of the corpus callosum and periventricular leukoencephalopathy as well as a hypoplastic corpus callosum, and defects in myelinization, in each patient, respectively. A review of the literature showed that, although non‐specific, ventriculomegaly, hydrocephalus, and cortical atrophy represent the most frequent imaging findings of brain anomalies in CFC syndrome. CNS abnormalities are significant diagnostic features of CFC syndrome and a brain MRI is recommended in individuals diagnosed with CFC or suspected of having CFC syndrome.

Human Placental Growth Hormone Is Increased in Maternal Serum in Pregnancies Affected by Down Syndrome

Objective: To evaluate the relationship between maternal serum levels of human placental growth hormone (hPGH) and fetal Down syndrome at gestational midtrimester. Methods: We retrospectively analyzed samples of serum from 21 women with Down syndrome pregnancies detected at gestational midtrimester. The samples were obtained at 16–23 weeks’ gestation during amniocentesis for fetal karyotyping. Sixty-two serum samples were used as controls, which were obtained at 16–23 weeks’ gestation from women with singleton, uncomplicated pregnancies, who gave birth to healthy neonates with a birth weight appropriate for gestational age. The hPGH levels were measured by a solid-phase immunoradiometric assay using 2 different epitopes. Results: The median hPGH values in the serum of the Down-syndrome-affected pregnancies were significantly higher (p < 0.05) than those of the normal pregnancies at 16–23 weeks’ gestation: the median value in the serum was 9.4 ng/ml (5th to 95th percentiles = 1.49–39.03) versus 4.7 ng/ml (0.53–7.88). Conclusion: The hPGH levels in maternal serum were found to be higher at 16–23 weeks’ gestation in pregnancies affected by fetal Down syndrome. Further investigation is needed to examine if maternal serum hPGH could be used as an additional marker in prenatal screening of Down syndrome at gestational midtrimester.

The A1555G mitochondrial DNA mutation in Greek patients with non-syndromic, sensorineural hearing loss

Mitochondrial DNA mutations are undoubtedly a factor that contributes to sensorineural, non-syndromic deafness. One specific mutation, the A1555G, is associated with both aminoglycoside-induced and non-syndromic hearing impairment. The mutation is considered to be the most common of all mitochondrial DNA deafness-causing mutations but its frequency varies between different populations. Here we report on the first large screening of the A1555G mitochondrial DNA mutation in the Greek population. The aim of this study was to determine the frequency of the A1555G mutation in Greek sensorineural, non-syndromic deafness patients, with childhood onset. We screened 478 unrelated Greek patients with hearing loss of any degree and found two individuals harboring the A1555G mutation (0.42%). Both cases had been subjected to aminoglycosides. They were prelingual, familial and homoplasmic for the A1555G mutation. One of the cases was also found heterozygous for the frequent GJB2 35delG mutation, while the other case was negative. The A1555G mutation seems to be less common than in other European populations.

Phenotype–genotype correlation of a patient with a “balanced” translocation 9;15 and cryptic 9q34 duplication and 15q21q25 deletion†

We report on a 2‐year‐old boy with intellectual disabilities, distinctive facies, hypotonia, cardiac, and renal malformations. During his infancy he had recurrent episodes of apnea, cyanosis, and bradycardia. Chromosomal analysis showed a de novo apparently balanced translocation 46,XY,t(9;15)(q31;q26)dn. The use of array‐comparative genomic hybridization (CGH) however, revealed the presence of additional cryptic complex chromosomal rearrangements involving a ∼5–5.8 Mb distal duplication on chromosome 9 (9q34.1 → 9q34.3), and deletions on three separate regions of chromosome 15 adding to ∼8.1–12.2 Mb (15q21.2 → 15q21.3, 15q22.31 → 15q23, 15q25.1 → 15q25.2). During confirmation with fluorescence in situ hybridization (FISH) an inversion was unexpectedly revealed on chromosome 15 (15q21.1 → 15q21.2). To our knowledge this is the first patient reported whose phenotype is due to partial trisomy 9q, and complex interstitial deletions of 15q, not involving the Prader–Willi/Angelman region and encompassing the critical region 15q21q25. We provide correlation between the clinical findings of our patient and the phenotype of the 9q34 duplication syndrome, the 15q21, and the 15q25 deletion syndromes.

Plasma Carnitine Levels of Pregnant Adolescents in Labor

STUDY OBJECTIVE To determine the concentration of plasma carnitine (total, free, and acylcarnitine) during the delivery of uncomplicated pregnancies of adolescent women. To investigate the relationship between maternal and neonatal levels of carnitine and to compare these carnitine levels between pregnant and nonpregnant adolescents. DESIGN Samples of maternal and umbilical blood were taken at the time of delivery and examined for the determination of the carnitine-total, free, and acylcarnitine-concentration by the use of an enzymatic-radioisotope method. Twenty-two cases of uncomplicated adolescent pregnancies with a normal labor and without perinatal complications were examined. The plasma level of carnitine was also examined in 17 healthy nonpregnant adolescent women, which constituted the control group. RESULTS The concentrations of plasma carnitine in adolescent pregnancies at the time of delivery were calculated at 19.6 +/- 2.15 microMol/L (total), 12.62 +/- 1.31 microMol/L (free), and 6.98 +/- 1.55 microMol/L (acylcarnitine). The corresponding mean values in umbilical plasma were 30.31 +/- 2.06 microMol/L, 22.39 +/- 1.64 microMol/L, and 7.92 +/-.96 mucroMol/L. There is a statistically significant difference between the mean values in maternal and umbilical plasma (P <.0001 for total and free carnitine and P <.012 for acylcarnitine). The correlations between adolescent pregnant women and their infants as regards total, free, and acylcarnitine were 0.137, 0.018, and 0.33, respectively. Neither of these parameters was statistically significant. The corresponding mean values of carnitine in nonpregnant adolescent women were statistically significantly higher than in adolescent pregnant women (total carnitine: 41.61 +/- 3.09 microMol/L, free: 31.39 +/- 2.81 microMol/L, acylcarnitine: 10.22 +/- 1.88 microMol/L, P <.0001). CONCLUSIONS The concentration of plasma carnitine at the end of adolescent pregnancy is low compared to the levels of umbilical carnitine at birth and that found in nonpregnant adolescent women. It may not have an obvious impact on the utilization of fatty acids in an uncomplicated full-term pregnancy; however, it suggests the potential risk for neonatal fatty-acid oxidation in a preterm or complicated pregnancy.

Prenatal Diagnosis of Trisomy 2 Mosaicism: A Case Report

We report a case of trisomy 2 mosaicism detected upon amniocentesis in a woman with advanced maternal age. A mos 47,XY,+2(4)/46,XY(21) karyotype was revealed using standard GTG banding. There were no pathological sonographic findings and the fetal size was normal for gestational age at 16th week. The use of serial high-resolution ultrasound examination of the fetus to detect major abnormalities was offered as an option to the parents who, however, decided for termination of the pregnancy. Fetal autopsy did not reveal any malformations. Trisomy 2 mosaicism is associated with variable phenotypic abnormalities without a specific pattern, intrauterine growth restriction, fetal demise or stillbirth. The rarity of trisomy-2 mosaicism in prenatal diagnosis, as well as the increased risk of an abnormal outcome makes the diagnostic approach and genetic counseling difficult.

3c syndrome with cryptorchidism and posterior embryotoxon

We report a case of the 3C (cranio-cerebello-cardiac) syndrome, also known as Ritscher–Schinzel syndrome, a rare autosomal recessive disorder characterized by craniofacial, cerebellar, and cardiac anomalies. In addition to features previously reported the child had Wormian bones of the skull, intra-abdominal testes, and posterior embryotoxon that have not previously been reported as part of the 3C syndrome.

Non Invasive Prenatal Diagnosis of Down Syndrome

Down syndrome (trisomy 21), which has an incidence of 1 in 800 live births, is considered to be the most frequent etiology of mental retardation and it is the predominant reason for women seeking prenatal diagnosis [Driscoll & Gross, 2009]. Trisomy 21 is used as a benchmark because it is the most common aneuploidy compatible with life and is associated with mental retardation and serious congenital anomalies. Currently used screening tests for aneuploidy are based on the assessment of fetal sonographic markers and/or the evaluation of biochemical markers in the maternal circulation during the first and second trimester. Screening test based on the combination of nuchal translucency assessment and biochemical markers at 11+0-13+6 weeks of gestation may detect 90-94% of pregnancies affected by Down syndrome at a false positive rate of 5% [Kagan et al., 2008]. The current gold standard for diagnosis of trisomy 21 is provided by invasive sampling of fetal genetic material through chorionic villus sampling (CVS) or amniocentesis followed by conventional cytogenetic or DNA analysis; however, both procedures are associated with an increased risk of fetal loss of about 1% and therefore they are recommended for pregnancies considered to be at high risk of fetal trisomy 21 [Alfirevic et al., 2003]. Since 1997, when cell free fetal DNA in maternal circulation was discovered, the research interest has focused on the development of reliable techniques for non-invasive prenatal diagnosis (NIPD) that would allow the direct analysis of fetal genetic material based on the discovery of cell-free fetal (cff) DNA and RNA in the maternal circulation. Current investigation fields of NIPD include fetal Rhesus D genotype determination in RhD negative women, fetal sex determination for sex-linked disorders and the role of cffDNA in pregnancy disorders such as preeclampsia but the holy grail of NIPD remains the detection of fetal aneuploidies [Honda et al., 2002; Bianchi et al., 2005]. The direct analysis of circulating fetal DNA for the NIPD of chromosomal aneuploidies is mainly complicated by the presence of the coexisting background maternal DNA. NIPD will hopefully overcome the limitations of the currently used methods for diagnosing Down syndrome antenatally and make prenatal testing safer for pregnant women and their fetuses. However, irrespective of which strategy is selected for isolating or distinguishing fetal genetic material in maternal plasma, the small quantity of cffDNA and cff mRNA poses severe technical challenges; all these issues should be addressed before the clinical application of these methods as screening test with high sensitivity, specificity and reproducibility.