Normal pregnancy- a state of insulin resistance.

BACKGROUND: Purpose of insulin resistance (IR) adapted by mother is to deliver enough quantity of nutrients to the growing fetus. Many maternal hormones and factors play role in causation of IR during pregnancy. AIM: The study aims at evaluating IR at different trimesters of pregnancy. MATERIALS AND METHODS: Pregnant women at 1(st), 2(nd) and 3(rd) trimester were grouped into groups I, II and III respectively (n=20 in each group). Healthy non-pregnant women were taken as controls (n=30). Fasting plasma glucose (FPG) and fasting serum insulin (FSI) were measured and IR indices such as fasting glucose to insulin ratio (FGIR), quantitative insulin sensitivity check index (QUICKI), log FSI and log HOMA1-IR were calculated. The student's t-test and one way Analysis of variance (ANOVA) were used for data analysis. RESULTS: The mean FSI, log FSI and log HOMA 1-IR were significantly higher in 2(nd) and 3(rd) trimesters while QUICKI was significantly lower in 2(nd) and 3(rd) trimesters of pregnancy when compared with controls. Also, mean FGIR was found to be significantly lower in 3rd trimester when compared with controls. CONCLUSION: As pregnancy advances, IR increases. Increased IR is associated with poor maternal and fetal outcome. Screening of all pregnancy for IR and early intervention may help to reduce the associated complications.

Cerebrospinal fluid free sialic acid and aspartate transaminase levels in meningitis.

BACKGROUND: Sialic acid (SA) is a nine carbon sugar derived from mannosamine and pyruvate. High levels of sialic acid and aspartate transaminase (AST) levels in cerebrospinal fluid have been described in pyogenic meningitis (PM) compared to tubercular meningitis (TBM). OBJECTIVES: To evaluate the levels of CSF free SA in PM and TBM and to assess the correlation between CSF free SA and CSF glucose or total protein levels. PATIENTS AND METHODS: A total of 122 subjects were studied and divided into children and adults. Further, these have been subdivided into controls, PM and TBM. CSF free SA was estimated by thiobarbituric acid assay of Warren and AST by Reitmann and Frankel method. RESULTS: CSF free SA and AST levels in children and adults were significantly high in PM (p<0.001) as compared to TBM and controls. CONCLUSION: A very high CSF free SA and AST were found to be characteristic of PM, making them useful parameters to differentiate PM from TBM.

Trisomy 18 in Kuwait.

BACKGROUND: Trisomy 18 (Edwards' syndrome, T18) is the second most common trisomy in man. We describe 118 children with regular T18 who were ascertained clinically and cytogenetically in the Kuwait Medical Genetics Centre during 1980-1997. METHODS: Ascertainment of T18 cases was performed shortly after birth. Chromosomal studies were carried out in addition to other relevant investigations. To investigate the factors associated with T18, a case-control study was carried out with 131 normal healthy newborns. Studied factors included maternal and paternal age, birth order, abortion, associated malformation, and survival. Multiple logistic regression analysis was used to adjust for confounding between variables. RESULTS: There was a preponderance of females among T18 cases (female:male ratio 2.1:1). The majority of T18 cases (53%) died before the second week of life. The most common associated anomalies were: congenital heart (38.1%) and gastrointestinal (25.4%). Multiplicity of malformations was also observed. Significant seasonal variation in T18 cases was detected with a peak in spring. Of the 118 T18 cases, 59 were delivered during 1994-1997 (average overall T18 birth prevalence rate 8.95 per 10 000 live births [95% CI: 6.66-11.23]). Concerning maternal age, 30.5% of the T18 cases' mothers were > or =35 years compared to 10.7% in the control group. The difference was statistically significant, P = 0.002. Logistic regression analysis showed that maternal age >30 years was a significant risk factor for T18, after adjusting for confounding with paternal age. Paternal age and abortion were not found to be significant risk factors. CONCLUSION: Trisomy 18 birth prevalence rate is high in Kuwait with advanced maternal age as a significant risk factor.

PIP: This paper describes associated factors of trisomy 18 (T18) or Edwards' syndrome among infants in Kuwait. A case control study of 131 normal newborn controls was undertaken. The study included information about gender, maternal age, paternal age, birth order, reproductive history, consanguinity, survival, and associated anomalies. Results showed a preponderance of females among T18 cases (female/male ratio, 2.1:1). The difference between the T18-case mothers and the control-group mothers was statistically significant (P = 0.002); however, there was no significant difference with regard to paternal age. The logistic regression analysis showed that the odds ratio for 2 abortions with reference to (0/1) abortion was 1.086, which is statistically significant as a risk for T18. The majority of children with T18 died before the second week of life. With regard to malformations, the most common associated anomalies were congenital heart and gastrointestinal abnormalities. Thus, the prevalence of T18 is high in Kuwait, with advanced maternal age as a significant risk factor.

De novo direct duplication 7p (p11.2-->pter) in an Arab child with MCA/MR syndrome: trisomy 7p a delineated syndrome?

A 3-year-6-month old Lebanese female child with multiple congenital anomalies including, facial dysmorphism, prominent low set ears, micrognathia, anti-mongoloid palpebral fissures and psychomotor retardation was investigated. Her karyotype showed de novo 46, XX, dir dup (7)(p11.2-->pter). The phenotypic manifestations in dir dup (7p) cases are briefly reviewed. Our observations in combination with other similar cases suggest that 7p trisomy due to dir dup (7p) can be regarded as a defined chromosome syndrome.

Recurrent regular trisomy-21 in two Bedouin families. Parental mosaicism versus genetic predisposition.

Two young, unrelated multiplex families with Bedouin ancestors, each confirmed to have 3 sibs with recurrent regular trisomy-21 are reported. Low grade mosaicism for trisomy-21 (3/350 cells) was confirmed in the mother in one of the families but not in the other. However, two of the relatives (first degree) were confirmed to have Down syndrome. The recurrence risk for trisomy-21 based on livebirth and prenatal diagnosis data were estimated at 1 to 2 percent for couples 35 years old or younger at the time of conception. However, such risk estimates are not available for recurrence of simple trisomy-21 to a particular couple (<35 years). Clustering of trisomy-21, trisomy-18 has been reported among Bedouins. The possibility of cryptic parental mosaicism as well as <> should be considered in genetic counselling of families with sibships of regular trisomy-21 or other aneuploidy.

Disease profile of 400 institutionalized mentally retarded patients in Kuwait.

In this preliminary report we summarize the results of a 4-year multidisciplinary systematic, etiological clinicogenetic survey of 400 institutionalized mentally retarded patients in Kuwait. All had an intelligence quotient below 50. A constitutional disorder, as the direct cause of the mental retardation, was found in 203 patients (50.75%)): a chromosomal abnormality in 37 (9.25%), Mendelian disorders in 137 (34.25%), MCA/MR in 22 (5.55%) and CNS malformations in 7 cases (1.75%). In 157 patients (39.35%) a pre-, peri or postnatal cause was ascertained. No etiological diagnosis was detected in 40 patients (10%). A detailed analysis of the "disease profile" is given and compared with the results of previous diagnostic genetic surveys among different institutionalized mentally retarded populations in Western and developing countries.

Familial pericentric inversion of chromosome 13, 46,XX,inv (13)(p13;q11): a new variant.

A 10-year-old female with right oblique inguinal hernia was investigated to exclude an XY karyotype. Chromosome analysis of peripheral blood showed 46,XX,inv(13)(p13;q11). In vitro aneuploidy was observed in two cells: a) 46,XX,inv(13), inv(13); b) 47,XX, +inv(13). Her father and three sisters were carriers for inv(13). Herein the authors review briefly familial inv(13)'s and report a new variant involving breakpoints (p13;q11).

The newly recognised limb/pelvis-hypoplasia/aplasia syndrome: report of a Bedouin patient and review.

A Bedouin infant born to consanguineous parents and grandparents is reported. She had Müllerian aplasia and the phenotypic features of the limb/pelvis-hypoplasia/aplasia syndrome (MIM 276820). Phenotypic variability of this newly recognised syndrome is briefly discussed.

Alagille syndrome with de novo del(20) (p11.2).

We report on an Arab boy with Alagille syndrome and a de novo deletion of the short arm of chromosome 20 with a 46,XY, del(20)(p11.2) chromosome constitution. Other reported cases are briefly reviewed.

Segregation of acrocentric chromosome association in familial dicentric Robertsonian translocation t(14p;22p), aneuploidy (trisomy-21) and heteromorphism.

The frequency and types of acrocentric chromosome association were quantitatively analysed in a Down syndrome child with unusual karyotype, 46, XX, -14, -22, t dic (14p;22p), +21, 21S+. Father and 4 sibs were heterozygous carriers for t dic (14p;22p). The variant 21S+ was inherited from the mother. The occurrence of translocation and trisomy in the same individual is extremely rare. Acrocentric chromosome association was analysed in this interesting family to understand the interrelationship of acrocentric chromosome association, Robertsonian translocation and heteromorphism, as possible predisposing factors for nondisjunction. Our findings suggest that acrocentric chromosome association is a heritable and nonrandom phenomenon. Heterozygous carriers for translocations and variants are likely to be at increased risk of nondisjunction. Long term family studies will enable to ascertain the causal-relationship of these factors more precisely.

Familial fragile secondary constriction on chromosome 2 (2q11) with unusual features and psychomotor retardation.

A child with fragile secondary constriction 2q11 associated with unusual clinical features and psychomotor retardation is described. The pathogenetic significance of this fragile site still remains unclear, and heterogeneity of clinical manifestations is not well understood.

Cytogenetic studies in a population suspected to have chromosomal abnormalities.

The present study describes the cytogenetic findings in cases suspected with chromosomal abnormalities, in cases of mental retardation, multiple congenital malformations, clinical features of Down's syndrome, Klinefelter's syndrome, Turner's syndrome, ambiguous sex, sterility, amenorrhea and history of repeated spontaneous abortions in couples. Cytogenetic studies were done in 144 of the total 205 cases. In all, 57 (39.58%) were shown to have chromosomal abnormality and of these, 34 cases (25.7%) were Down's syndrome. Sex chromosome abnormality was found in 19 cases (13.2%). The results confirm the significant contribution of chromosomal abnormalities in the genesis of mental retardation, and abnormal sexual development.

Down syndrome in Kuwait.

During a 7-year-period (1980-1986) trisomy 21 was confirmed in 635 cases (257 males and 278 females). There were 611 cases of trisomy 21 (96.2%), 12 of different translocations (1.9%), 9 of mosaicism (1.4%), and 3 with nonclassical karyotypes (0.5%). The frequency of chromosome aberrations in our study is compared to that of major world-wide cytogenetic surveys comprising 17,738 Down syndrome cases. These surveys showed that regular trisomy 21 constitutes 92.9%, translocations 4.3%, mosaicism 2.2%, and nonclassical karyotypes 0.5%.

Mosaicism 45,X/46,X, t dic(Xp:Xp) in a girl with short stature.

An eight-year-old girl with marked short stature and no apparent stigmata of Turner syndrome was investigated. Clinical features include bilateral epicanthic folds, frontal bossing, prominent ears and normal intelligence. Ultrasound scanning revealed an apparently normal vagina, streak ovaries and no uterus. Bone age was normal. Karyotype analysis of peripheral blood lymphocytes showed mos 45,X/46,X tdic(Xp:Xp) in the ratio 66:34, respectively. In addition, three cells with different abnormal X chromosomes were present which possibly originated from a 46,XX clone. Replication of the duplicated X chromosome was consistently late and symmetrical. Buccal smear confirmation of the karyotype showed Barr body negative in 90% and large or bipartite in 10% of the cells. Karyotypes of the parents were normal. The clinical manifestations in cases of Xp deletion due to terminal rearrangement associated with or without a 45,X cell line are discussed.

Familial manic-depressive illness with deleted short arm of chromosome 21: coincidental or causal?

A 35-year-old Arab lady and her mother, both with bipolar manic-depressive illness and 46,XX,21p-(pcen----pter), are reported. The clinical significance of this association is considered.