Cytogenetic abnormalities and herdetiry thrombophilias among the abortees: study of 1000 couples

Recurrent miscarriage affects only 1% of all couples. It is one of the most frustrating experiences for both patients and clinicians. The present study aimed at studying: the role of cytogenetic abnormalities and hereditary thrombophilias in repeated pregnancy losses [RPL], and the associated risk factors. Kuwait Medical Genetics Centre A cross section study for cytogenetic abnormalities followed by a nested case control was conducted for 1000 couples referred because of RPL. A control group was selected at random from female patients attending the outpatient clinics for a reason other than abortion for comparison with those who were proved to have chromosomal abnormalities. Asubgroup of 100 female partners, who had no cytogenetic abnormalities, were further tested for the presence of factor V Leiden [FVL; Arg506Gln] and prothrombin [FII] gene mutations [G20210A]. the prevalence of chromosomal abnormalities was 4.4%; most of them were structural aberrations [79.5%] represented mainly by inversion and translocation. Carriers of FVL mutation [G1691A] among the patient's group was significantly higher than that of the control group [10% vs. 2% respectively].One patient was heterozygous for FII G20210A mutations. This was nearly the same like that found in controls. The percentage of consanguineous marriages among patient group was less than that among the control group. Chromosome study for couple who have had RPL must be carried out. For complete and proper workup we have to investigate the presence of FVL, and FII G20210A mutations among patients with normal karyotype

XX male: a report of two unrelated cases and review of literature

Two unrelated phenotypically males with 46,XX karyotype are presented. The first patient is 5.5 year old who presented with congenital undescended testis while the other patient is 35 year old who has infertility since 6 years. Hormonal profile of the second patient is consistent with hypergonadotrophic hypogonadism with low testosterone level. The first patient's profile revealed a picture consistent with 21-hydroxylase deficiency. FISH technique using [Quint-Essential-Y-specific DNA probe] specific for Yp11.2 region was applied on metaphase spreads revealed the presence of Yp11.2 sequence on the short arm of the X chromosome in the second patient while it was absent in the first patient. DNA analysis of both patients using SRY gene amplification revealed the existence of SPY gene in the second patient and absence of the gene in the first patient. The possible underlying mechanisms for sex reverse in both cases are discussed

Genotype-phenotype correlation among patients with dystrophinopathies

To correlate the site and size of dystrophin gene deletion with the clinical picture in patients with dystrophinopathies. The dystrophin gene is one of the largest known genes. More than half of the dystrophinopathy cases are associated with intrageneic deletions. The importance of the study arises from the fact that dystrophin cDNA probes provide a direct method of genetic diagnosis. This is the first study in an Arab population and only the second to use a three multiplex PCR method. Kuwait Medical Genetic Centre and Faculty of Medicine -Ain Shams University, Egypt Fifty-two patients with dystrophinopathies [50 with Duchenne muscular dystrophy [DMD] and 2 with Becker muscular dystrophy [BMD] from both Kuwait and Egypt were ascertained. Dystrophin gene deletions were detected using three multiplex reactions. DNA analysis showed that 71.4% of the patients had deletion of the dystrophin gene while 28.6% showed no deletion. 24.5% had two deleted exons while 14.3% had only one deleted exon. The most common deleted exons among the Kuwaiti patients were 81,45 and 48 while exons 19, 45, 48 and 51 were found more commonly deleted among the Egyptian patients. The onset of walking was not changed by the number of exons deleted except when five exons were deleted. However, delayed onset of walking was observed when exon 48,51 and 45 were deleted [r=0.6078, and p=0.110]. On the other hand, the average onset of weakness was neither correlated to the number of the exons deleted or to the deletion sites. Similar results were obtained regarding the average onset of wheel chair dependency. There was a slightly lower IQ with deletion of exons 48,45 and 12 but in general there is no correlation between the IQ and the site or the frequency of the deletion. Study of the intragenic deletions in 25 exons of the dystrophin gene using three different multiplex PCR sets revealed that 78%, 76% and 12% of DMD patients had deletion of each of the three sets separately. With all three sets together, the detection of deletion rate was increased to 86%. Fifty percent of the deleted exons were located in the distal hot spot, 8% in the proximal hot spot while 42% were scattered over both sides of the hot spot. No significant correlation was found between the size/site of the dystrophin deletions and the clinical severity. A multi centre larger study is recommended for a better understanding of the genotype-phenotype correlation

Clinico - genetic study of dystrophinopathies: a comparative study between Kuwait and Egypt

Duchenne and Becker muscular dystrophies [DMD and BMD] are one of the most common X-Linked disorder in human which are caused by mutations of the dystrophin gene located on the X chromosome. This study was carried out in both Kuwait and Egypt. Fifty two patients with dystrophinopathies were examined from both Kuwait and Egypt in order to [1] study some characteristic features of those patients and [2] identify gene deletions among them. Twenty six patients were selected randomly from both Kuwait and Egypt A special questionnaire including all relevant data was designed for this study. All patients were subjected to all relevant investigations including DNA analysis and muscle biopsy analyzed with three dystrophin monoclonal antibodies. The statistical package for social science [SPSS], Z test, Chi square test and Student t test were used for statistical analysis. There was a significant difference between the Kuwaiti and Egyptian patients regarding maternal age [P<0.005] but not for paternal age. The onset of walking was delayed in 40.6% of the cases while the onset of weakness was noticed in 19.3% of the Kuwaiti patients before 2 years of age. Wheel chair dependency was observed in 88.8% between the age 7-12 years. In both groups 82% have an IQ above 70 and 26% had lQ above 100. ECG abnormalities were seen in 77.8% of the patients. DNA analysis showed that 71.4% of the patients had a deletion in the gene while 28.6% had no deletion. Two deleted exons were found in 24.5% and 14.3% had only one deleted exon. The most common deleted exons among Kuwaiti patients were 8, 45, 48 while exons 19, 45, 48 and 51 were deleted more commonly in the Egyptians. Better identification, neonatal screening and DNA examination are urgently needed for precise diagnosis. Proper genetic counseling and prenatal diagnosis are strongly recommended for prevention and management

Clustering of trisomy 18 in Kuwait: genetic predisposition or environmental?

This study describes 59 newborns with regular trisomy 18 [Edwards' syndrome, T18] who were ascertained clinically and cytogenetically at the Kuwait Medical Genetic Centre from 1994 to 1997, out of 118 T18 cases identified from 1980 to 1997. Materials and T18 cases were ascertained clinically and cytogenetically shortly after birth. In addition to assessing the T18 birth prevalence rate and confidence limits during the years 1994-1997, we investigated the possible etiological factors by a case-control study with normal healthy newborns. Studied factors included gender, parental age, birth order, abortion, clinical variables [presentation, amniotic fluid and mode of delivery], and survival. The average T18 birth prevalence rate during the period was 8.95 per 10,000 live births [95% confidence limits 6.66-11.23]. The T18 cases were mostly females, with a male:female ratio of 1:2.1, and the majority [53%] died before the second week of life. Maternal age above 30 years was found to be a significant factor for T18. This high T18 birth prevalence rate suggests clustering of T18 in the highly inbred population of Kuwait. Such clustering may indicate a possible environmental, and to a lesser extent, genetic predisposition to aneuploidy nondisjunction

Trisomy 18 in Kuwait: a study of two decades

One hundred and eighteen patients with regular Trisomy 18 [T18] were ascertained clinically and cytogenetically in the Kuwait Medical Genetics Centre. The aim of this study was to provide an overview of T18 cases in Kuwait and highlight some associated factors, [out of the ascertained 118 T18 cases, 59 were delivered during the period 1994-1997]. The overall incidence rate during the years 1994 to 1997 was 9/10,000 livebirths [95% confidence interval 6.7 to 11.2 per 10,000 livebirths], which is considered high. The male:female ratio among T18 cases was 1:2.1. To investigate the factors associated with T18, a group-matched case-control study was undertaken which included 131 normal healthy controls. The mean maternal age of the T18 patients' mothers [31.9 years] was significantly higher [p=0.002] than the controls' mean maternal age [27.1 years]. Abnormal presentation was recorded in 14.4% in T18 cases compared to 5.4% in controls, while the mode of delivery was abnormal in 43.2% of cases [90% of them were cesarean section] compared to 15.3% in controls, [p<0.001]. Polyhydramnios occurred in 9.3% of the T18 cases versus 1.5% in controls, [p<0.001]. Significant seasonal variation in T18 cases was detected with a peak in spring [March-May], [p<0.05]. The most common anomalies observed were congenital heart [38.1%], gastrointestinal malformations [25.4%], limb anomalies [24.6%], microcephaly [20.3%], omphalocele [11%], eye anomalies 11% and genital anomalies [9.3%]. Multiplicity of malformations was noticed: [24.6% had only one malformation, 24.6% had two malformations, 17.8% had 3 malformations and 9.3% had 4 malformations]. In conclusion, the T18 incidence rate in Kuwait is high with possible associated factors of advanced parental age, polyhydramnios, abnormal presentation and mode of delivery

Complete testicular feminization syndrome with 47,XYY karyotype: adouble hit phenomenon

A phenotypic female patient 18 years old primary amenorrhea, absent uterus, male serum testosterone level, and 47, XYY karyotype is discussed. An ultrasound scanning of the pelvic organs revealed the absence of uterus, and a laparoscopy confirmed the ultrasound findings. Laparotomy and bilateral gonadectomy were also performed. Histopathological study of both gonads showed that each was formed of small testicular tubules lined by sertoli cells without spermatogenic elements. Neither vas nor epididymis were identified macroscopically or microscopically. These findings are consistent with the complete form of testicular feminization syndrome in association with 47, XYY karyotype

Familial left handedness

This study is part of a study of left handedness among preparatory school students in Alexandria during the scholastic year 1992-1993, aiming to study the familial aggregation of left handedness among left handed students. The overall prevalence of left handedness was 2.65% but, if we put in consideration all left handed family members, the prevalence of left handedness would increase to 15.4%, with a range that varies from 13.9% to 16.78 and 16.8, when both parents are right handed, the father is left handed, and the mother is left handed, respectively. The prevalence of familial left handedness [29.28%] differs according to the sex of left handed parent. It is most frequent when both parents were left handed, frequent when the mother is left handed, and less frequent when the father is left handed. This finding reflects the genetic role played at least in some families with left handedness, and the maternal effect and/or genomic imprinting

Left handedness among preparatory school students in Alexandria

In order to study left handedness among school students, 13636 students were included to estimate the prevalence of left handedness among the Alexandria preparatory school. The overall prevalence of left handedness was 2.65%. left handedness in male sex [3.12%] was higher than in female sex [2.19]. bilateral handedness was found in 0.06%. the prevalence of consanguinity among left handed group [19.61] was more than that among the right handed group [16.49%]. Left handed mothers were found in 7.73% of left handed group and 1.89% in the control group. The prevalence of left handed relatives among the left handed students was 32.87% compared with 19.19% in the right handed students. The scholastic achievement among the left handers was more or less similar to that among the right handed with no significant difference

Holoprosencephaly clustering in Kuwait

Seven patients with holoprosencephaly were ascertained clinically and cytogenetically at the Kuwait Maternity Hospital out of 16121 total deliveries making an incidence of 4.3/10000 total births which is almost 4 folds that of the previous years. The male to female sex ratio was 1.3/1. The mean maternal age was 29 [range 26-33], the mean paternal age 31 [range 28-43] consanguinity was recorded in two cases .and prematurity in five cases. All cases were sporadic except one family, case 4 who has 2 affected sibs with cebocephalic type of Holoprosencephaly. Chromosomal study was normal in all cases except case 2 has variant in [Y]

Down syndrome in sibs: a study of recessive hypothesis controlling nondisjunction

In the highly inbred Kuwaiti population, 7 unrelated families each has 2 sibs with regular trisomy 21 were studied. The aim was to test the presence of autosomal recessive gene controlling nondisjunction in man. Among them males were predominant [male/female ratio 1.8/1], the mean [ +/- standard error] maternal and paternal ages were 30.9 [ +/- 1.S62] and 37.5 [ +/- 2.635] years respectively. Parental consanguinity was no Eed in two families, while maternal parent consanguinity was observed in one family. Abortion was detected once in two families. Parental chromosome study was normal except one with l6qh + [parental]. Application of Dahlberg's equation and the complete ascertainment method provided no enough evidence to exiude the presence of an autosomal recessive gene controlling nondisjunction in man

Holoprosencephaly: counselor dilemma

Three unrelated families having Holoprosencephaly [HP] in the index case were reported with different situations leading to counsellor dilemma. The first family has an unusual heritable balanced chromosome translocation. The second and third families follow a possible autosomal dominant and autosomal recessive modes respectively. This situations reflects the genetic heterogeneity of this disorder which complicates the counseling process

Effect of parental age, birth order and consanguinity on nondisjunction in the population of Kuwait

401 patients with numerical chromosomal aberrations were detected from 1980 to 1983 and studied to determine the effect of parental age, seasonal variation, birth order and consanguinity on nondisjunction. For purposes of comparison 403 phenotypically normal newborns were selected. The study showed a significant association between maternal age, paternal age and consanguinity with nondisjunction. No seasonal variation was detected. Application of the Mantel Haenszel chi square test revealed an intensified maternal age effect as paternal age advances. The significant association between consanguinity and nondisjunction in the present study may raise the possibility of a multifactorial mode of inheritance

Syndromal and nonsyndromal cleft lip with or without cleft palate in Kuwait

This study involved 166 patients cleft lip with or without cleft palate ascertained at the Kuwait Medical Gentre between 1984 and 1986. The 1985 and 1986 incidence rates were 1.51/1000 and 1.56/1000 livebirths, respectively. The male/female ratio was 1:1.15. Consanguinity was found in 44.6%. Most of the cases [90.4%] were sporadic, while 9.6% were familial. Single cleft lip was detected in 40.4%, cleft plate in 9.6%, and combined cleft lip and cleft plate in 50.0%. Isolated clefting was recorded in 44.0%, while clefting associated with known syndromes was recorded in 36.1%, and 19.9% were undiagnosed. A chromosomal aberration was found in 9.0% of patients; autosomal recessive etiology was noted in 5.4%, autosomal dominant 6.0%, multifactorial 41.0%, environmental 1.8%, and genetically uncertain or undetermined in 36.7%