Emese Horváth

Four years experience of first-trimester nuchal translucency screening for fetal aneuploidies with increasing regional availability

Background. A prospective screening study was carried out at the regional genetic and perinatal center in South Hungary in order to determine the efficiency of first‐trimester nuchal translucency screening for fetal aneuploidies, following augmentation of the availability of nuchal translucency screening in the region by the inclusion of newly‐trained hospital sono‐graphers.

Leiden mutation, bed rest and infection: Simultaneous triggers for maternal deep-vein thrombosis and neonatal intracranial hemorrhage?

The possible etiologic roles of infection and bed rest are discussed in connection with a case of maternal homozygous Leiden mutation leading to prematurity, maternal deep-vein thrombosis and neonatal intracranial hemorrhage in a heterozygous premature baby. Maternal bacterial infection and bed rest may trigger deep-vein femoral thrombosis in women with a homozygous Leiden mutation on tocolytic therapy for the treatment of premature labor. The neonate carrying at least one mutated allele of factor V Leiden might be at risk for the development of intracranial hemorrhage.

Fetomaternal Transfusion and Pregnancy Outcome after Cordocentesis

Objective: To study the extent of fetomaternal transfusion and the outcome of pregnancy after cordocentesis. Material and Methods: 268 women underwent percutaneous fetal umbilical cord blood sampling for fetal karyotyping between 15 and 26 gestations of weeks. Complete follow-up was available in 221 (82.5%) of the cases. Cordocentesis was performed under continuous real-time ultrasound guidance. The duration of the procedure and the post-procedural bleeding time was counted in seconds. Fetomaternal transfusion was calculated by using the measurements of the maternal serum levels of α-fetoprotein before and after the procedure. The data were analyzed by Student’s t and multiple regression tests. Results: The maximum and mean amounts of fetomaternal transfusion were 1.067 and 0.061 ml, respectively. Twenty percent or more α-fetoprotein elevation was in 35.4% of the cases. Positive correlation was found between bleeding time after cordocentesis and fetomaternal transfusion (r = 0.174, p < 0.0129) as well as between the duration of the procedure (r = 0.165, p < 0.0171) and the amount of fetomaternal transfusion. Comparing the cordocentesis at the placental insertion site and at the free cord loop, a smaller amount of fetomaternal transfusion was observed (p < 0.0123) in the latter. Transplacental passage was associated with a higher amount of fetomaternal transfusion (p < 0.0067). No association was found between the extent of fetomaternal transfusion and the outcome of pregnancy. The fetal loss related to the cordocentesis was 0.50%. Conclusions: The extent of fetomaternal transfusion was influenced by the subsequent four parameters: procedural time, bleeding time, puncture site and transplacental penetration. The lack of the association between the degree of fetomaternal transfusion and the outcome of pregnancy, along with the low (0.50%) post-procedural fetal loss rate, suggest that cordocentesis is clinically a safe procedure.

Nasal bone length:prenasal thickness ratio: a strong 2D ultrasound marker for Down syndrome

To evaluate the feasibility of incorporating two‐dimensional ultrasound measurements of nasal bone length (NBL) and prenasal thickness (PT) into the second‐trimester anomaly scan and to determine whether the NBL : PT ratio could help in differentiating euploid and Down syndrome fetuses.

Early detection of Angelman syndrome resulting from de novo paternal isodisomic 15q UPD and review of comparable cases.

BackgroundAngelman syndrome is a rare neurogenetic disorder that results in intellectual and developmental disturbances, seizures, jerky movements and frequent smiling. Angelman syndrome is caused by two genetic disturbances: either genes on the maternally inherited chromosome 15 are deleted or inactivated or two paternal copies of the corresponding genes are inherited (paternal uniparental disomy). A 16-month-old child was referred with minor facial anomalies, neurodevelopmental delay and speech impairment. The clinical symptoms suggested angelman syndrome. The aim of our study was to elucidate the genetic background of this case.ResultsThis study reports the earliest diagnosed angelman syndrome in a 16-month-old Hungarian child. Cytogenetic results suggested a de novo Robertsonian-like translocation involving both q arms of chromosome 15: 45,XY,der(15;15)(q10;q10). Molecular genetic studies with polymorphic short tandem repeat markers of the fibrillin-1 gene, located in the 15q21.1, revealed that both arms of the translocated chromosome were derived from a single paternal chromosome 15 (isodisomy) and led to the diagnosis of angelman syndrome caused by paternal uniparental disomy.ConclusionsAS resulting from paternal uniparental disomy caused by de novo balanced translocation t(15q;15q) of a single paternal chromosome has been reported by other groups. This paper reviews 19 previously published comparable cases of the literature. Our paper contributes to the deeper understanding of the phenotype-genotype correlation in angelman syndrome for non-deletion subclasses and suggests that patients with uniparental disomy have milder symptoms and higher BMI than the ones with other underlying genetic abnormalities.

Identification of a novel missense GLRA1 gene mutation in hyperekplexia: a case report

IntroductionHereditary hyperekplexia is a neurological disorder characterized by excessive startle responses with violent jerking to noise or touch, stiffening of the trunk and limbs, clenching of the fists and attacks of a high-frequency trembling. Hyperekplexia has a heterogeneous genetic background with several identified causative genes and demonstrates both dominant and recessive inheritance. Mutations in the glycine receptor alpha 1 subunit gene occur in about 30 percent of hyperekplexia cases.Case presentationIn this study, we report the case of a Hungarian boy whose abnormal movements, muscle stiffness and convulsions were first noted when he was 4 days old. Neurological and electrophysiological investigation suggested the clinical diagnosis of hyperekplexia.ConclusionsDirect sequencing of the coding regions and the flanking introns of the glycine receptor alpha 1 subunit gene revealed a novel heterozygous missense mutation (c.211A/T, p.Ile71Phe). Genetic screening of our patient’s family revealed that the clinically unaffected parents and sister do not carry the mutation, suggesting that the identified sequence change is a de novo mutation. Since hyperekplexia can have severe consequences, including sudden infant death due to laryngospasm and cardiorespiratory failure, identification of the causative genetic alteration(s) of the disease is high priority. Such knowledge is necessary for prenatal diagnosis, which would allow informed family planning and greater parental sensitivity to hyperekplexia 1-associated risks.

Nemaline myopathy type 2 (NEM2): two novel mutations in the nebulin (NEB) gene.

Nemaline myopathy is a type of the heterogeneous group of congenital myopathies. Generalized hypotonia, weakness, and delayed motor development are the main clinical features of the typical congenital form. Histopathology shows characteristic nemaline rods in the muscle biopsy. Mutations in at least 7 genes, including nebulin gene (NEB), proved to be responsible for this muscle disease. We present a boy with nemaline myopathy type 2 (NEM2) caused by compound heterozygosity for 2 novel mutations, a deletion and a duplication in the NEB gene. The deletion was inherited from the father and the duplication from the mother. Testing all family members supports genetic counseling.

OP34.03: Prenasal thickness, nasal bone length and their ratio: good second trimester sonographic markers for Down syndrome

Objectives: Our aim was to determine the accuracy of a novel simple scoring system based on sonographic markers in differentiating between low and high risk forplacenta accreta (PA). Methods: All women who were referred to the Sheba Medical Center due to suspected PA were included, underwent a detailed ultrasound examination. A score was given based on the common sonographic findings of PA: loss of the hypoechoic retroplacental zone and placental lacunae. A score of 0–2 was defined as low risk and 3 was defined as high risk. Patients assigned to the high risk category underwent prophylactic pelvic artery catheterization before cesarean section and embolization if needed, whereas patients in the low risk category underwent simple cesarean section. Results: 71 women were included. PA was diagnosed clinically during surgery in 28 women, of whom 31 had a score of 3, and ruled out in 43 women, of whom only one had a score of 3. The sensitivity, specificity, positive predictive value and negative predictive value of our ultrasound-based scoring system in predicting PA were 90%, 97.5%93 and 95% respectively. Conclusions: A simple scoring system based on ultrasound alone can identify accurately a high risk population for PA who can benefit from prophylactic pelvic artery catheterization and embolization.

Increased nuchal translucency and decreased fetomaternal transfusion after chorionic villus sampling

To investigate the relationship between nuchal translucency (NT) and fetomaternal transfusion (FMT) after chorionic villus sampling (CVS).

Difficulties of genetic counselling in rare, mainly neurogenetic disorders

INTRODUCTION In recent decades methods used for the investigation of the genetic background of rare diseases showed a great improvement. AIM The aim of the authors was to demonstrate difficulties of genetic counselling and investigations in case of five rare, mainly neurogenetic diseases. METHOD During pre-test genetic counselling, the disease suspected from the clinical symptoms and the available genetic tests were considered. During post-test genetic counselling, the results of the genetic tests were discussed. RESULTS In three of the five cases genetic tests identified the disease-causing genetic abnormalities, while in two cases the causative abnormalities were not identified. CONCLUSIONS Despite a great improvement of the available genetic methods, the causative genetic abnormalities cannot be identified in some cases. The genetic counsellor has a key role in the assessment and interpretation of the results and in helping the family planning.