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D Chitayat

Publications and source records attributed to D Chitayat.

At least 37 records · Page 2Linked to original sources
PubMed2001

Role of amniotic fluid interphase fluorescence in situ hybridization (FISH) analysis in patient management.

We retrospectively reviewed 309 amniotic fluid interphase fluorescence in situ hybridization (FISH) analyses performed from October 1995 to June 1999 to assess the role of interphase FISH in the management of patients at increased risk for fetal aneuploidies. Gestational age and indications for amniocentesis, clinical interventions after FISH results, as well as interventions after final culture reports were analyzed. There were 244 (79%) normal, 50 (16%) abnormal and 15 (5%) inconclusive FISH results. There were no false-positive or false-negative results, but there were nine (3%) clinically significant chromosomal abnormalities not detectable by FISH. Of the 50 women with abnormal FISH results, 26 (52%) elected to terminate the pregnancy prior to the availability of the standard chromosome analysis. In two of the fetuses with trisomy 21 no abnormalities were reported by ultrasound examination. Our experience indicates that interphase FISH results played an important role in decision making, especially for pregnancies close to 24 weeks' gestation. Standard karyotype analysis is still required for detection of chromosome abnormalities not detectable by interphase FISH techniques and for clarification of unusual or inconclusive FISH results.

Amniotic Fluid↗
PubMed2001

A 1.5 million-base pair inversion polymorphism in families with Williams-Beuren syndrome.

Williams-Beuren syndrome (WBS) is most often caused by hemizygous deletion of a 1.5-Mb interval encompassing at least 17 genes at 7q11.23 (refs. 1,2). As with many other haploinsufficiency diseases, the mechanism underlying the WBS deletion is thought to be unequal meiotic recombination, probably mediated by the highly homologous DNA that flanks the commonly deleted region. Here, we report the use of interphase fluorescence in situ hybridization (FISH) and pulsed-field gel electrophoresis (PFGE) to identify a genomic polymorphism in families with WBS, consisting of an inversion of the WBS region. We have observed that the inversion is hemizygous in 3 of 11 (27%) atypical affected individuals who show a subset of the WBS phenotypic spectrum but do not carry the typical WBS microdeletion. Two of these individuals also have a parent who carries the inversion. In addition, in 4 of 12 (33%) families with a proband carrying the WBS deletion, we observed the inversion exclusively in the parent transmitting the disease-related chromosome. These results suggest the presence of a newly identified genomic variant within the population that may be associated with the disease. It may result in predisposition to primarily WBS-causing microdeletions, but may also cause translocations and inversions.

Adolescent↗
PubMed2001

First-trimester increased nuchal translucency and fetal hypokinesia associated with Zellweger syndrome.

We report the prenatal detection of increased nuchal translucency and decreased fetal movements, at 11 weeks of gestation, in a fetus at risk for Zellweger syndrome. The diagnosis of Zellweger syndrome was confirmed by metabolic studies on cultured chorionic villus sampling (CVS) cells and the pregnancy was terminated. The couple's subsequent pregnancy was monitored using the same method. In this pregnancy the nuchal translucency measured at 12 weeks' gestation was normal, the fetus was active, and biochemical studies using CVS and amniocentesis confirmed normal results. We believe this to be the first reported case of Zellweger syndrome followed prenatally in which an increased nuchal translucency and fetal hypokinesia were detected in the first trimester. During the pregnancy with the affected child the maternal serum screen (MSS) showed low estriol level. We believe this to be the second report of a low estriol level on MSS in a pregnancy affected with Zellweger syndrome.

Adult↗
PubMed2000

A partial deficiency of interleukin-7R alpha is sufficient to abrogate T-cell development and cause severe combined immunodeficiency.

Both in vitro and in vivo studies established that interleukin 7 (IL-7) is essential for differentiation of immature T cells and B cells but not natural killer (NK) cells in the mouse. In humans, although both T-cell and B-cell progenitors express the functional IL-7 receptor that consists of IL-7R alpha and the gamma common (gamma c) chain, this lymphocyte receptor system is critical for T lineage but not for B lineage development. Indeed, complete gamma c deficiency like IL-7R alpha deficiency results in the arrest of T-cell but not B-cell development (T(-)B(+) SCID). However, partial deficiency of gamma c caused by missense mutations results in a T(+)B(+) phenotype and a delay of clinical presentation. It was therefore plausible to assume that partial deficiency of IL-7R alpha, like partial gamma c deficiency may lead to a milder clinical and immunologic phenotype. A P132S mutation in the IL-7R alpha was identified in 3 patients with severe combined immunodeficiency (SCID) within an extensively consanguineous family. Substitution of proline with serine in the extracellular portion of IL-7R alpha did not affect IL-7R alpha messenger RNA (mRNA) and protein expression, but severely compromised affinity to IL-7, resulting in defective signal transduction. In response to IL-7 stimulation, Jak-3 phosphorylation was markedly reduced in both patient cells as well as in COS cells reconstituted with mutant IL-7R alpha. Surprisingly, this partial deficiency of IL-7R alpha resulted in a severe phenotype, including markedly reduced circulating T cells while sparing B-cell numbers similar to gamma c chain deficiency. However, unlike the previously reported cases, serum immunoglobulins were virtually absent. Further, unlike gamma c deficiency, NK cell numbers and function was preserved. Despite the partial deficiency, clinical presentation was indistinguishable from a complete gamma c deficiency, including severe and persistent viral and protozoal infections and failure to thrive. Unlike partial gamma c deficiency, a partial deficiency of IL-7R alpha results in an arrest of T-cell development, leading to typical severe combined immunodeficiency. This underscores the critical role of IL-7R alpha chain in the differentiation of T cells. (Blood. 2000;96:2803-2807)

Agammaglobulinemia↗
PubMed2000

Inverted duplication of the distal short arm of chromosome 3 associated with lobar holoprosencephaly and lumbosacral meningomyelocele.

A fetus with lobar holoprosencephaly and lumbosacral meningomyelocele associated with duplication of the short arm of chromosome 3 is reported. The anomalies were detected on fetal ultrasound at 20 weeks' gestation and the autopsy findings correlated well with the prenatal findings. The fetal karyotype was 46,XY,der(3)del(3)(p26) dup(3)(p26p21.3). The association of holoprosencephaly with duplication 3p is well known, but to the best of our knowledge this is the first reported association of meningomyelocele with 3p duplication. These findings suggest that a gene or genes with a crucial role in central nervous system development are located on the short arm of chromosome 3.

Abnormalities, Multiple↗
PubMed2000

De novo 46,XX,t(6;7)(q27;q11;23) associated with severe cardiovascular manifestations characteristic of supravalvular aortic stenosis and Williams syndrome.

Supravalvular aortic stenosis may present as an isolated finding or as part of Williams syndrome. Williams syndrome is a contiguous gene syndrome associated with neurodevelopmental and multisystemic manifestations caused by hemizygous deletion at 7q11.23. We report on the prenatal and histopathological findings in a patient with a chromosome translocation involving the Williams syndrome critical region. The initial abnormality on fetal ultrasound was hydrops fetalis detected at 30 weeks and echocardiography showed narrowing of the aorta and the pulmonary arteries. The baby died shortly after delivery and an autopsy revealed diffuse tubular thickening with luminal narrowing of the aorta, aortic branches, and the pulmonary arteries. Histopathology showed dysplasia of the media with reduced elastic content and "cartwheel" arrangement of collagen, elastic, and muscle fascicles. The karyotype was 46,XX,t(6;7)(q27;q11.23). Three signals were detected using the Oncor fluorescent in situ hybridization probe for elastin-Williams syndrome (WSCR) suggesting that the break in chromosome 7 is within the elastin-Williams gene. This patient is of special interest because of the prenatal presentation and the chromosomal translocation involving the elastin-Williams syndrome locus.

Aortic Valve Stenosis↗
PubMed2000

Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies.

BACKGROUND: Corticosteroids are first-line drugs for the treatment of a variety of conditions in women of childbearing age. Information regarding human pregnancy outcome with corticosteroids is limited. METHODS: We collected prospectively and followed up 184 women exposed to prednisone in pregnancy and 188 pregnant women who were counseled by Motherisk for nonteratogenic exposure. The primary outcome was the rate of major birth defects. A meta-analysis of all epidemiological studies was conducted. The Mantel-Haenszel summary odds ratio was calculated for the pooled studies with 95% confidence intervals. A cumulative summary odds ratio was also calculated by combining studies in chronological order. Chi-squared for homogeneity was determined to establish the comparability of the studies. RESULTS: In our prospective study, there was no statistical difference in the rate of major anomalies between the corticosteroid-exposed and control groups. In the meta-analysis, the Mantel-Haenszel summary odds ratio for major malformations with all cohort studies was 1.45 [95% CI 0.80, 2.60] and 3.03 [95% CI 1.08, 8. 54] when Heinonen et al. ('77) was removed. This suggests a marginally increased risk of major malformations after first-trimester exposure to corticosteroids. In addition, summary odds ratio for case-control studies examining oral clefts was significant (3.35 [95% CI 1.97, 5.69]). CONCLUSIONS: Although prednisone does not represent a major teratogenic risk in humans at therapeutic doses, it does increase by an order of 3.4-fold the risk of oral cleft, which is consistent with the existing animal studies.

Abnormalities, Drug-Induced↗
PubMed2000

Basal lamina abnormality in the skeletal muscle of Walker-Warburg syndrome.

The basal lamina of skeletal muscle fibers has been reported to be thinned and disrupted in patients with Fukuyama and laminin-alpha-2-deficient congenital muscular dystrophies. The basal lamina is normal in other, later-onset, muscular dystrophies, but the plasma membrane is disrupted. It is unknown whether the dystrophic process in Walker-Warburg syndrome (WWS) is characterized by a basal laminal abnormality, a sarcolemmal abnormality, or both. The present study examined the skeletal muscle of a 3-month-old patient with WWS by immunohistochemistry and electron microscopy and compared the findings with control muscle samples. In control samples the basal lamina of skeletal muscle fibers was a continuous, uniformly dense structure associated with sarcolemma. In WWS the basal lamina appeared deranged, with disruptions in nonnecrotic muscle fibers. Furthermore, in some fibers the basal lamina was thinner, and in others, it was duplicated. Dystrophin, laminin-alpha-2, and adhalin stains revealed normal immunoreactivity. The disruptions in the basal lamina may play a primary role in the degeneration of muscle fibers in WWS. When compared with the dystrophies with a primary sarcolemmal defect, it appears that those with primary basal lamina abnormalities (WWS, laminin-alpha-2-deficient, and Fukuyama congenital muscular dystrophies) present early in life, and the phenotype is more severe.

Basement Membrane↗
PubMed2000

Genetic counselling in prenatally diagnosed non-chromosomal fetal abnormalities.

Advances in technology and skills have resulted in the improved detection of fetal ultrasound abnormalities by ultrasound. In addition, the development of new diagnostic methods has resulted in major advances in our ability to detect microscopic and submicroscopic chromosome abnormalities as well as single gene disorders. This often enables us to provide the family with accurate information regarding the aetiology, prognosis, the risk of recurrence and the prenatal diagnosis options available in future pregnancies. Genetic counselling is important because this information should be communicated to the family in simple language, with care and sensitivity, so that the family can make decisions that are fully informed.

Congenital Abnormalities↗
PubMed2000

Fetal cardiac dextroposition in the absence of an intrathoracic mass: sign of significant right lung hypoplasia.

We reviewed our experience of fetal cardiac dextroposition in the absence of an intrathoracic mass. Ten cases were found by fetal echocardiography to have a normal cardiac axis, but the heart was shifted into the right chest and the amount of right lung tissue was reduced. At birth seven of the infants had confirmed structural heart disease (70%), including three with scimitar syndrome. Two infants had additional extracardiac anomalies (20%). Seven infants born at term had clinical pulmonary hypertension with a diagnosis of right lung hypoplasia in all of them. Two neonates died owing to significant heart disease (one with scimitar syndrome and the other with hypoplastic left heart syndrome). Of the three pregnancies that were terminated, the two fetuses with autopsies had severe right lung hypoplasia. Fetal cardiac dextroposition and right pulmonary artery hypoplasia in the absence of an intrathoracic mass are important signs of right lung hypoplasia, which can be associated with significant pathologic cardiac and extracardiac conditions.

Dextrocardia↗
PubMed1999

Early-infantile galactosialidosis: prenatal presentation and postnatal follow-up.

Galactosialidosis (GS) is an autosomal recessive condition caused by combined deficiency of the lysosomal enzymes beta-galactosidase and alpha-neuraminidase. The combined deficiency has been found to result from a defect in protective protein/cathepsin A (PPCA), an intralysosomal protein which protects these enzymes from premature proteolytic processing. The most severe form of GS, the early-infantile form, results in early onset of edema, ascites, visceromegaly, and skeletal dysplasia. We report a case of early-infantile GS in a male infant who presented with nonimmune fetal hydrops (NIH), "coarse" facial appearance, massive fluid-filled inguinal hernias, multiple telangiectasia, and diffuse hypopigmentation; he subsequently developed visceromegaly. The diagnosis of GS was confirmed biochemically and the defect in PPCA characterized at the protein level. Examination of fetal peripheral blood smears sampled at 30 weeks gestation demonstrated vacuolation of lymphocytes, suggesting blood film examination may be a useful screening tool for cases of NIH where a metabolic disorder is suspected. Skeletal radiography at birth demonstrated punctate epiphyses of the femora, calcanei, and sacrum. We present a discussion of and differential diagnosis for this radiographic finding. To the best of our knowledge, this is the first case of early-infantile GS presenting with stippled epiphyses.

Blotting, Western↗
PubMed1999

Compound heterozygosity for the Achondroplasia-hypochondroplasia FGFR3 mutations: prenatal diagnosis and postnatal outcome.

We report on a male newborn infant, a compound carrier of heterozygous mutations in the FGFR3 gene causing achondroplasia and hypochondroplasia. The mother has achondroplasia and carries the common G1138 (G380R) mutation in the FGFR3 gene; the father has hypochondroplasia due to the C1620A (N540K) mutation in the same gene. The fetus was found to carry both mutations diagnosed prenatally by amniocentesis at 17.6 weeks of gestation, following maternal serum screening which showed an increased risk for Down syndrome (1:337). Detailed fetal ultrasound studies showed a large head, short limbs, and a small chest at 22 weeks of gestation. The changes were more severe than those of either achondroplasia or hypochondroplasia. The patient was born by cesarean section at 38 weeks of gestation and had rhizomelic shortness of the upper and lower limbs with excess skin folds, large head, enlarged fontanelles, frontal bossing, lumbar gibbus, trident position of the fingers, and a narrow chest with a horizontal line of demarcation at the narrowest area of the chest. Skeletal radiographs showed shortness of the long bones and flare of metaphyses. He had respiratory difficulties and was treated with nasal prongs. Seizures developed on day 2 of life and recurred on day 9 and responded to treatment with phenobarbital. Brain computed tomographic scan showed possible grey matter heterotopia, partial agenesis of the corpus callosum, and cortical dysplasia. To our knowledge, there are only two previously published cases of compound heterozygous achondroplasia-hypochondroplasia patients. The diagnosis was confirmed by DNA mutation analysis of the FGFR3 gene in both cases.

Abnormalities, Multiple↗
PubMed1999

Fragile X premutation is a significant risk factor for premature ovarian failure: the International Collaborative POF in Fragile X study--preliminary data.

The preliminary results of an international collaborative study examining premature menopause in fragile X carriers are presented. A total of 760 women from fragile X families was surveyed about their fragile X carrier status and their menstrual and reproductive histories. Among the subjects, 395 carried a premutation, 128 carried a full mutation, and 237 were noncarriers. Sixty-three (16%) of the premutation carriers had experienced menopause prior to the age of 40 compared with none of the full mutation carriers and one (0.4%) of the controls. Based on these preliminary data, there is a significant association between fragile X premutation carrier status and premature menopause.

Adolescent↗
PubMed1999

Congenital toxoplasmosis: prenatal diagnosis, treatment and postnatal outcome.

We report a female patient with congenital toxoplasmosis who presented with hydrops fetalis and cerebral abnormalities, detected on fetal ultrasound. Following prenatal treatment, the hydrops fetalis resolved and at four months of age she has normal growth and development. This case emphasizes the potential good prognosis in cases with congenital toxoplasmosis detected and treated prenatally.

Adult↗
PubMed1999

Anesthesia for Freeman-Sheldon syndrome using a laryngeal mask airway.

PURPOSE: To present a case of Freeman-Sheldon syndrome (FSS) with a previously unreported technique of anesthetic management, consisting of a malignant hyperthermia free anesthetic and laryngeal mask airway. CLINICAL FEATURES: Freeman-Sheldon syndrome (also known as whistling face syndrome, Windmill-Vane-Hand syndrome, cranio-carpo-tarsal dysplasia and distal arthrogryposis type 2) is a rare congenital disorder defined by facial and skeletal abnormalities. The three basic abnormalities are microstomia with pouting lips, camptodactyly with ulnar deviation of the fingers and talipes equinovarus. Patients with FSS frequently present for surgical correction of musculoskeletal or facial abnormalities. There are several anesthetic challenges including difficult airway, intravenous cannulation and regional technique. They may be at increased risk for malignant hyperthermia and postoperative pulmonary complications. We present a case of a two-year-old child with FSS undergoing elective unilateral inguinal hernia repair. A non-triggering anesthetic technique was used, consisting of 2 mg x kg(-1) propofol followed by a continuous infusion, nitrous oxide 50%/oxygen, and 3 microg x kg(-1) fentanyl. Intraoperative and postoperative analgesia was provided by an ilioinguinal nerve block with 10 ml bupivacaine 0.25% with epinephrine 1:200,000. The airway was maintained with a #2 laryngeal mask airway. The anesthetic was uneventful and there were no signs or symptoms of malignant hyperthermia. The patient was discharged home later the same day in good health. CONCLUSION: The use of a laryngeal mask airway and non-triggering anesthetic technique should be considered as options for anesthetic management in patients with FSS for short procedures that do not require neuromuscular blockade.

Anesthesia, Inhalation↗
PubMed1999

Mosaicism for a small marker chromosome resulting from a familial Robertsonian translocation (21;22).

A mosaic marker chromosome found in amniotic fluid was shown to have originated from the proximal part of the long arm of chromosome 22. This marker is unusual because it is the result of a deletion of a maternally inherited Robertsonian 21;22 translocation. It is suggested that the deletion and marker formation probably occurred post zygotically in the fetus. This rare case illustrates the difficulty in estimating risk of fetal abnormalities associated with de novo marker chromosomes. In this example, although the 'extra' marker chromosome contains euchromatin, the karyotype may still be 'balanced'.

Adult↗