R. Scarinci

Chromosome 18 aberrations and epilepsy: A review

Epilepsy is commonly observed in patients with chromosomal aberrations. We evaluated epilepsy and electroencephalographic (EEG) features in a group of patients carrying aberrations of chromosome 18. Fourteen patients were recruited: five with an 18p deletion syndrome (18pDS); six with an 18q deletion syndrome (18qDS); two with trisomy 18p syndrome; and one with a 45,XY,t(17‐18) (cen‐q11.2) karyotype. Patients with 18pDS had neither epilepsy nor EEG anomalies; four patients with 18qDS had epilepsy with partial seizures occurring during infancy or early childhood. Partial seizures were also present in both patients with trisomy 18p. By contrast, mixed seizures were observed in the patient carrying a translocation between chromosomes 17 and 18. Our data and a re‐evaluation of the literature suggest that epilepsy is infrequent in patients with 18pDS. Conversely, partial seizures and focal EEG anomalies may be observed in those with patients with 18qDS. Our observations suggest that the haplo‐insufficiency of genes located on the long arm of chromosome 18 is more likely to be associated with epilepsy, than is haplo‐insufficiency of genes located on the short arm. While further EEG/clinical investigations are needed to validate these observations, this study indicates a possible relationship between chromosome 18 genes and epilepsy.

Epilepsy and electroencephalographic anomalies in chromosome 2 aberrations. A review.

UNLABELLED Epilepsy and electroencephalographic (EEG) anomalies are common in subjects carrying chromosomal aberrations. We report clinical and EEG investigations on 13 patients carrying chromosome 2 anomalies, including two patients with inversions, six with translocations, two with partial duplications and three with interstitial deletion syndromes. Epilepsy and/or EEG anomalies were found in one patient with a chromosome 2 translocation, in both of those carrying partial duplications and in all three with interstitial deletion syndromes. No epilepsy or EEG anomalies were detected in the remaining patients. CONCLUSIONS Epilepsy may be associated with chromosome 2 aberrations. Gross rearrangements involving the long arm of chromosome 2 might be more often associated with epilepsy than those involving the short arm. The association of epilepsy with chromosome 2 duplications is less clear. In particular, our observations and a review of the literature appear to suggest that a strict relationship between epilepsy and interstitial deletions involving the 2q24-q31 region. In the latter disorder tonic and focal seizures occur early in life. Generalized and focal myoclonic jerks tend to appear in infancy and are subsequently followed by seizures mixed in type. Seizures usually persist up to late childhood and are drug resistant. Further studies are necessary to better define the electroclinical patterns of patients carrying deletions in 2q24-q31. These may help to direct systematic study of this--probably underestimated--cause of severe epilepsy.

Association of microphthalmia and esophageal atresia: Description of a patient and review of the literature

Since 1988, when Rogers first described a boy with anophthalmia associated with esophageal atresia, eight similar cases have been reported. These patients lend support to the hypothesis that this association of congenital anomalies constitutes a discrete entity, although the etiology is still unknown.We report a patient with this combination of malformations as well as a marked hypoplasia of the entire left half of the body.

Neurocutaneous syndrome with mental delay, autism, blockage in intracellular vescicular trafficking and melanosome defects

We evaluated a 11‐year‐old male patient with mental delay, autism and brownish and whitish skin spots. The former resembled those of neurofibromatosis, the latter those of tuberous sclerosis. The patient received a complete clinical work‐up to exclude neurofibromatosis, tuberous sclerosis, or any other known neurocutaneous disease, with biochemistry, chromosome analysis and analysis of skin specimens. Being all the other tests not significant, two main ultrastructural defects were observed. The first was a blockage in intracellular vescicular trafficking with sparing of the mitochondria; the second an aberrant presence of melanosomes in vacuoles of several cell lines and abnormal transfer of these organelles to keratinocytes. This patient presented with a unique clinical picture distinct from neurofibromatosis or tuberous sclerosis or any other known neurocutaneous disease. The ultrastructural abnormalities suggested a defect in cell trafficking involving several cell lines and compartments.

New neurocutaneous syndrome with defect in cell trafficking and melanosome pathway: The future challenge

OBJECTIVE Case study of a CNS impairment lacking in presumptive cause; case presents with a clinical phenotype encompassing multiple differently expressed and combined symptoms, as well as a subtle skin defect. MATERIALS AND METHODS A 6-year-old male with apparently isolated mental delay, speech delay, attention deficit/hyperactivity disorder, epilepsy, and subtle and insignificant skin dyschromias. The patient underwent a systematic evaluation, including clinical history; medical, neurological and ophthalmologic examinations. Skin, teeth, nails, hair and sudation were examined for defects. Routine laboratory tests for blood, urine, were performed. The proband had thyroid function tests, electrocardiography, genitourinary system and abdominal examinations. Special examinations pertaining to mental performance, biochemistry, chromosome studies, imaging and electrodiagnostic studies, and skin biopsy were also performed. RESULTS Investigators ruled out genetic syndromes, congenital infections, fetal deprivation, perinatal insults, intrauterine exposure to drug abuse, and postnatal events such as CNS infections as possible common causes of brain impairment. Being all further test negative, the patient exhibited an ultrastructural defect of the skin, identical to that previously described [Buoni S, Zannolli R, de Santi MM, Macucci F, Hayek J, Orsi A et al. Neurocutaneous syndrome with mental delay, autism, blockage in intracellular vesicular trafficking and melanosome defects. Eur J Neurol 2006;13:842-51], suggesting that some cell compartments, such as rough endoplasmic reticulum, lysosomes, Golgi apparatus, and the vesicular zone (racket) of Birbeck granules, sharing similar components, can be altered, resulting in a common defect in cell trafficking, associated to melanosome defects. CONCLUSIONS This new devasting, ultrastructural phenotype accompanied by apparently unspecific and mixed neurological symptoms should represent a future challenge to finally discover the pathogenesis of many childhood CNS symptoms, that currently seem to lack any apparent cause.

OC282: Amniotic fluid isoprostane levels in fetuses with cystic hygroma

included sensitivities, false-positive rates and receiver–operating characteristic (ROC) curves. Results: Of 576 pregnancies studied from 1995 to 2006, 145 (25.2%) were affected. At 12–13 weeks’ gestation, fetal cardiomegaly predicted the affected pregnancies significantly better than placentomegaly (area under ROC curve, 0.949 vs. 0.687, P < 0.05). The sensitivity for prediction of the affected pregnancies was 90.6% for fetal cardiomegaly (CTR ≥ 0.5), 69.8% for placentomegaly (PT > 18 mm) and 65.1% for combined testing. The corresponding false-positive rate was 6.8%, 50.3% and 2.8% respectively. At 14–15 weeks’ gestation, the sensitivity for prediction of affected pregnancies was 93.8% for fetal cardiomegaly, 93.8% for placentomegaly and 87.5% for combined testing. The corresponding false-positive rate was 16.7%, 76.9% and 17.7% respectively. MCAPSV was not predictive in early second trimester. However, at 18–19 weeks’ gestation, MCAPSV (at a cut-off 1.5 multiples of the median) predicted affected pregnancies significantly better than fetal cardiomegaly (area under ROC curve, 0.959 vs. 0.788, P < 0.05). The sensitivity for the prediction of affected pregnancies was 100.0% for fetal cardiomegaly and 57.1% for high MCAPSV while the corresponding false-positive rate was 46.2% and 0% respectively. Conclusions: The best ultrasonographic predictor of affected pregnancies at 12–13 weeks’ and 18–19 weeks’ gestation was fetal CTR and MCAPSV respectively.

P08.05: Intrauterine oxidative stress and Doppler flussimetry in fetuses with IUGR

notch and clinical risk factors were present in 41.9% and 11% of women respectively. There were statistically significant differences between Doppler indices from pregnancies with or without subsequent PE or associated complications: mean PI 1.75 vs 2.04 (P = 0.002, t-Student test) and mean RI 0.75 vs 0.79 (P = 0.000, t-Student test). A multivariate logistic regression produced a two parameter model (including the mean PI and the presence of clinical risk factors) with the best sensitivity (46.27%) and specificity (80.99%) for the prediction of PE and its associated complications. Conclusion: There are differences in uterine Doppler blood flow indices at 11–14 weeks in pregnancies with or without subsequent PE and /or associated complications. The combination of mean PI with the presence of clinical risk factors at this gestational age show the best sensitivity and specificity for the prediction of PE and its associated complications in our population.

P03.27: Fetal defects and increased nuchal translucency thickness

Results: In 40 euploid fetuses and 34 aneuploid fetuses 159 measurements of JLS volume and NT thickness were analyzed. The volume of JLS and gestational age showed a quadratic relation (p < 0.01) with a maximum size at 96 days. The maximum volume of the JLS was larger in fetuses with aneuploidy compared to euploidy (3.54 vs. 0.96 cm3) and the JLS were longer present (range 43 vs. 30 days). Time lag analysis revealed that enlargement of the NT preceded an increase in volume of the JLS (p < 0.001) in all fetuses. Conclusion: Increased NT is associated with a disturbed lymphatic development in which NT enlargement precedes enlargement of JLS. Aneuploid fetuses seem to have a more severe disturbance of lymphatic development.

P15.05: The use of 3‐4D ultrasound improves the diagnosis of spinal dysraphism

Objectives: To assess the feasibility of prenatal diagnosis and the outcome of partial agenesis (PACC) and hypoplasia of corpus callosum (HCC). Methods: PACC/HCC were suspected on fetal multiplanar neurosonography when the corpus callosum appeared caudally shorter and thinner respectively. Follow-up was obtained in all cases. Results: Between 1990–2003, 8 cases of PACC and 3 cases of HCC were identified at a median gestational age of 22 weeks (21–33) (see table). The cavum septi pellucidum was present in 9 cases, in 7 there was mild to severe ventriculomegaly, usually in association with ‘teardrop’ lateral ventricles, and 4 had associated cerebral anomalies (Dandy-Walker complex, emimegalencephaly, microcephaly). Magnetic resonance (MR) was performed in 4/11 cases without adding significant information. Five fetuses were terminated, 7 had multiple anomalies, and 3 are developing normally. Conclusions: PACC can be reliably diagnosed since midgestation. However, multiplanar neurosonography is required. On standard axial planes sonographic findings are similar to complete agenesis but more subtle. In particular the cavum septi pellucidum is usually present. MR did not offer significant advantage over multiplanar neurosonography. HCC was an incidental finding usually in fetuses with multiple anomalies. The outcome of PACC/HCC is similar to complete agenesis of the corpus callosum.

P052: Can a selective use of amniocentesis replace the routine for advanced maternal age?

Objective: To determine the feasibility of correctly identifying fetal gender from 11 to 13 weeks of gestation. Methods: Fetal gender assessment by ultrasound was prospectively carried out in 425 singleton pregnancies at 11–13 weeks of gestation (confirmed by crown-rump length or biparietal diameter) immediately before chorionic villus sampling for karyotyping. A total of 425 women underwent a detailed assessment of fetal anatomy at 11–13 weeks of gestation by means of transabdominal and transvaginal sonography. Fetal gender was identified in transverse and sagittal planes, and was confirmed by chorionic villus sampling. Results: The accuracy of sex determination increased with gestation from 91.7% at 11 weeks, to 97.2% at 12 weeks and 100% at 13 weeks. Male fetus were wrongly assigned as female in 5.5% of cases in 11 weeks, 2.4% at 12 weeks and 0% at 13 weeks. The accuracy of correctly identifying fetal gender increased with gestational age. Conclusion: Whilst the accuracy of sonographic determination of fetal gender at 11–13 weeks is good, our decision on invasive testing for sex-linked conditions should be undertaken.