Mitochondrial DNA mutations in two bulgarian children with autistic spectrum disorders.

Autism is a neurodevelopmental disorder of unknown origin that manifests in early childhood. Autism spectrum disorders (ASDs) refer to a broader group of neurobiological conditions, pervasive developmental disorders. Despite several arguments for a strong genetic contribution, the molecular basis in most cases remains unexplained. Several studies have reported an association between ASDs and mutations in the mitochondrial DNA (mtDNA) molecule. In order to confirm these causative relationship, we screened 21 individuals with idiopathic ASDs for a number of the most common mtDNA mutations. We identified two patients with candidate mutations: m.6852G>A that produces an amino acid change of glycine to serine in the MT-CO1 gene and m.8033A>G (Ile→Val) in the MT-CO2 gene. Overall, these findings support the notion that mitochondrial mutations are associated with ASDs. Additional studies are needed to further define the role of mitochondrial defects in the pathogenesis of autism.

Mental retardation in childhood: clinical and diagnostic profile in 100 children.

Mental retardation (MR) is present in 2-3% of individuals in the general population, either as an isolated finding, or as part of an underlying disorder. It is the reason for a substantial part of referrals of patients and families to the pediatric genetic counseling units. MR may be genetically determined, or due to environmental (including perinatal) influences. Despite the thorough examination, physicians often are unable to define the etiology, in at least 30-50% of cases. This report presents the experience with 100 consecutive children with mental retardation, admitted to the Section of clinical genetics of the University pediatric hospital in Sofia over one year period. According to the routinely used classification, the patients' disease states have been subgrouped into genetic (35), multifactorial (3), environmental (3), and of unknown etiology (59). The research protocol included careful dysmorphologic, neurologic and developmental assessment, as well as cytogenetic, biochemical and molecular genetic testing. The rate of the diagnostic yield of the whole group was 41%. The discussion includes clinical examples and literature reports.

Mesomelic form of chondrodysplasia and congenital glaucoma associated with de novo translocation (13;18)(q14;q23).

Mesomelic form of chondrodysplasia and congenital glaucoma associated with de novo translocation (13;18)(q14:q23): Mesomelic dysplasias are characterized by limb shortening most prominent of the middle segment of the extremities (forearm and lower leg). In addition to several syndromic forms a few patients with sporadic or familial forms and without precise nosological classification have been reported so far. In this report we present a young female with disproportionate mesomelic dwarfism, dysmorphic facial features, bilateral glaucoma, patent ductus arteriosus, low and hoarse voice, and generalized muscular hypotonia. At the age of 2.5 years mental development is normal. High resolution G-banded chromosome studies revealed a de novo reciprocal translocation with karyotype 46,XX t (13;18)(q14;q23). The concurrence of this de novo autosomal translocation with this distinct phenotype supports the hypothesis that disruption of (a) gene(s) at the translocation breakpoints causes this unusual, apparently new form of skeletal chondrodysplasia.

[Second trimester Down syndrome serum screening--results from a pilot study]. / Serumen skrining za sindrom na Daun vuv vtori trimestur na bremennostta--rezultati ot pilotno prouchvane.

The results from a pilot prospective study--second trimester Down syndrome [DS] serum screening between 15 and 21 w.g. with two markers (alpha-fetoprotein and free bb-hCG)--were summarised. Sensitivity, false-positive rate [FPR], positive predictive value [PPV] of the screen positive and negative predictive value [NPV] of the screen negative result for the sbgroups II and below 35 years of age were analysed. The uptake for invasive prenatal testing in screen positive patients and the percentage of terminated pregnancies with prenatally diagnosed DS fetuses as well as the ratio "lost unaffected pregnancies/1 DS fetus diagnosed antenatally" were also calculated. High sensitivity of the DS serum screening was achieved--75% and 87.5% in the subgroups below and II the age of 35 respectively with 6.6 and 31.7% FPR. With higher DS age risk the PPV of the screen positive test was higher and the NPV of the screen negative result--lower. The percentage of invasive prenatal testing in screen positive patients was high (average 83.4%) without significant differences in the two age subgroups. Pregnancy was terminated in all cases with antenatally diagnosed DS fetuses. The ratio "lost unaffected pregnancies/1 DS fetus diagnosed antenatally" for serum screening was lower compared to the same ratio when screening by age. The results from our pilot study (serum screening sensitivity and FPR, uptake for invasive testing in screen-positive cases) are comparable to the ones reported in literature. This is an important prerequisite for introduction of mass DS screening for our population.

[Pregnancy complications with abnormal results of biochemical screening for Down syndrome in second trimester and normal fetal karyotype]. / Uslozhneniia na bremennostta pri abnormni rezultati ot biokhimichnite skriningovi testove za sindrom na Daun vuv vtori trimectur i normalen kariotip na ploda.

Pregnancy complications were studied in the following groups of pregnancies with structurally and chromosomally normal fetuses: 1) 216--with elevated free beta-hCG above 2 MoM and 134--above 2.5 MoM; 2) 37--with elevated alpha-fetoprotein [AFP] above 2 MoM; 3) 67 screen-positive patients below the age of 35. The following complications were compared in the studied and the control groups: preterm delivery and premature rupture of membranes [PROM], preeclampsia (in general and severe one), IUGR without preeclampsia, delivery of small for gestational age [SGA] and low birth weight [LBW] infants and perinatal fetal loss. Pregnancy outcome in cases with free beta-hCG above 2 MoM was not different from that in the control group. With 2.5 cut-off level the incidence of preeclampsia and of LBW infants was higher in the studied than in the control group. Elevated AFP above 2 MoM alone was associated with more frequent preeclampsia including severe one (in all the latter cases--IUGR present). In the screen-positive group the incidence of preeclampsia (in general and severe one with IUGR), SGA and LBW infants and perinatal mortality rate were significantly higher than in the control group. No difference was found between the studied and the control groups regarding subsequent development of IUGR without preeclampsia, preterm delivery and PROM. Abnormal second trimester serum screening test results (elevated free beta-hCG or AFP alone above 2.5 and 2 MoM respectively) in pregnancies with normal fetal karyotype indicate higher risk for subsequent development of preeclampsia. Screen-positive patients, being a heterogeneous group (including ones with elevated free bb-hCG alone and ones with elevated both free beta-hCG and AFP), are at increased risk for other pregnancy complications too.

[The indirect echographic signs in the prenatal diagnosis of spina bifida aperta in the second trimester of pregnancy. A report on 2 cases]. / Indirektni ekhografski priznatsi pri prenatalna diagnostika na spina bifida aperta vuv vtoriia trimestur na bremennostta. Prinos na dva sluchaia.

The authors present a brief literary review on the frequency and etiological factors of the opened spinal dysraphism. The importance of its echographic diagnosis is indicated by using indirect signs, mainly microcephaly, ventriculomegaly, cerebellar pathology ("a sign of the banana") and characteristic fronto-temporal configuration of the fetal encephalic cranium ("a sign of the lemon") up to 24 week's of gestation. Two cases of diagnosed spinal dysraphism during the second trimester of pregnancy with established indirect echographic signs, promoting active search for direct echographic image of this congenital defect of the neural tube, are described.

[Percutaneous cholecystectomy and litholysis with methyl tert-butyl ether under ultrasonic control]. / Perkutanna kholetsistektomiia i litoliza s metil-tretichen butileter pod ultrazvukov kontrol.

The first percutaneous cholecystostomies under ultrasound control with therapeutic purpose, performed in Bulgaria, are reported. They furnish the opportunity for local treatment of acute cholecystitis and chemical litholysis in biliary calculosis. Control of the latter was realized by microscopic determination of the amount of cholesterine crystals in periodically aspirated bile. Indications for this procedure are defined after thorough discussion by internist and surgeon. Transhepatic approach and long-term treatment with methyltertiary-butyl ether are considered obligatory.

[Typical and atypical resections of the liver with 2 clinical cases]. / Vurkhu tipichnite i atipichnite rezektsii na cherniia drob s prinos ot dve klinichni nabliudeniia.

The development of resection liver surgery is discussed in a historical aspect. The basic topographic-anatomical guidelines, indications and different techniques of performance of atypical and typical liver resection are given. Two clinical cases of spacious liver resections are reported: resection of large hydatid cyst of the left lobe in a 16 years old girl and two liver resection for liver cystadenocarcinoma in a 25 years old woman. The advantages of applying top technical achievements in liver resection surgery are pointed out.