Sanjad-Sakati syndrome/Kenny-Caffey syndrome type 1: a study of 21 cases in Kuwait.

We studied 21 patients with Sanjad-Sakati syndrome (SSS) from 16 families. Parental consanguinity was recorded in 2 families (12.5%). All patients had severe intrauterine growth retardation, short stature, small hands and feet, blue sclera, deep-set eyes, microcephaly, persistent hypocalcaemia and hypoparathyroidism. Medullary stenosis was detected in 2 patients. Cytogenetic and fluorescent in situ hybridization studies were normal. All affected persons had homozygous deletion of 12 bp (155-166del) in exon 3 of the TBCE gene. All of the parents were heterozygous carriers of this mutation. The high frequency of SSS and low frequency of consanguineous marriages in this study may reflect a high rate of heterozygous carriers.

Primary male infertility in Kuwait: a cytogenetic and molecular study of 289 infertile Kuwaiti patients.

Infertility is one of the major public health problems, affecting 15% of couples who attempt pregnancy; in 50% of these, the male partner is responsible. Chromosomal abnormalities and Y microdeletions in the azoospermia factor (AZF) region are known to be associated with spermatogenetic failure. In the present study, 289 patients with primary male infertility because of spermatogenetic failure were studied in order to highlight the molecular background of male infertility in Kuwait, and to avoid the possibility of transmission of any microdeletions/chromosomal aberrations to offspring via intracytoplasmic sperm injection (ICSI). Of the 289 infertile men, 23 patients (8%) had chromosomal aberration in the form of Klinefelter syndrome/variant (16/23; 69.6%), XYY syndrome (3/23; 13%), XX male syndrome (2/23; 8.7%), 45,X/46X, i(Yp)(1/23; 4.4%) and 45,XY, t(9;22) (1/23;4.4%). Y-chromosome microdeletion in the AZFb and AZFc regions were detected in 7/266 cases (2.6%). Testicular biopsy was carried out in 31 azoospermic patients, of whom five men had Sertoli-cell only syndrome, while 26 patients had spermatogenic arrest. In conclusion, this study showed that the frequency of both chromosomal anomalies and Y microdeletions were found in 10.4% of the infertile men. The potential risk of transmitting these genetic disorders to offspring provides a rationale for screening infertile men prior to ICSI.

A morpho-etiological description of congenital limb anomalies.

BACKGROUND: Limb anomalies rank behind congenital heart disease as the most common birth defects observed in infants. More than 50 classifications for limb anomalies based on morphology and osseous anatomy have been drafted over the past 150 years. The present work aims to provide a concise summary of the most common congenital limb anomalies on a morpho-etiological basis. PATIENTS AND METHODS: In a retrospective study, 70 newborns with anomalies of the upper and/or lower limbs were ascertained through clinical examination, chromosomal analysis, skeletal surveys and other relevant investigations. RESULTS: Fetal causes of limb anomalies represented 55.8% of the cases in the form of 9 cases (12.9%) with chromosomal aberrations (trisomy 13, 18 and 21, duplication 13q and deletion 22q) and 30 cases (42.9%) with single gene disorders. An environmental etiology for limb anomalies was diagnosed in 11 cases (15.7%) as amniotic band disruption, monozygotic twin with abnormal circulation, vascular disruption (Poland sequence, sirenomelia and general vascular disruption) and an infant with a diabetic mother. Twenty cases (28.5%) had limb anomalies as part of sporadic syndromes of unknown etiology. CONCLUSIONS: The morpho-etiological work-up of limb anomalies adopted in the present study is valuable for detecting the cause of the anomaly and is crucial for its prevention. Prevention can be achieved by proper genetic counseling, which includes recurrence risk estimation and prenatal diagnosis.

Fragile X syndrome: a clinico-genetic study of mentally retarded patients in Kuwait.

In a prospective study in Kuwait, 182 mentally retarded male patients who fulfilled 5 or more clinical criteria of fragile X syndrome were screened using polymerase chain reaction (PCR) testing. Twenty patients (11%) were highly suspected of having fragile X syndrome due to mutation at the FRAXA locus; none had mutation at the FRAXE locus. Of these, 11 (55%) were confirmed fragile-X-positive by both cytogenetic and PCR techniques. The most frequent clinical features were: prominent forehead, high arched palate, hyperextensible joints, long ears, prominent jaw, height > 10th centile and attention-deficit hyperactivity. Less common were avoidance of eye contact (45%), autism (45%) and seizures (30%). Large testes were found in 55% of cases. Pre-pubertal and post-pubertal clinical criteria were different.

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.

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

BACKGROUND: This study describes 59 newborns with regular trisomy 18 (EdwardsA centAA 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 METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Indoor air pollution and acute lower respiratory infections in the first two years of life.

The relationship between outdoor air pollution and acute respiratory infections (ARI) was previously documented. There are recent indications for connection between indoor air pollution and ARI in infants and young children. The aim of this study was to identify the relationship of indoor air pollutants to acute lower respiratory infection (ALRI) in children (< 2 years). The indoor air pollutants concentrations were measured in the homes of the sample. The sample consisted of 115 children (< 2 years) representing the control group (24), ALRI but no pneumonia (24), pneumonia (30), severe pneumonia or very severe disease (37). Air sampling was performed to measure the concentration of total suspended particulates (TSP), SO2 and CO. These pollutants were found in higher concentrations in cases' homes (52.46 +/- 19.68 microg/m3, 298.15 +/- 669.37 microg/m3, and 1.92 +/- 3.60 ppm) than in controls' homes (31.92 +/- 8.76 microg/m3, not detected, and 0.33 +/- 1.63 ppm respectively). Whereas SO2 was detected only in houses using kerosene, TSP and CO were detected with the different types of cooking fuels. Their mean concentrations were highest for biomass (88.86 +/- 13.30 microg/m3 and 9.29 +/- 2.50 ppm) and lowest for gas (40.78 +/- 15.25 microg/m3 and 0.76 +/- 2.19 ppm). Measures to improve indoor air quality are highly required.

Central pulverulent (Coppock) cataracts. A sibship of two Arab females with full-cousin normal parents.

Two Arab (Saudi) sisters are described each with bilateral typical central pulverulent (powdery) or Coppock cataracts. As their unaffected parents are first cousins, the heredity is probably autosomal recessive, unlike the autosomal dominant heredity of the vast majority of previously described cases in the literature. Chromosomes were normal in all four individuals. There are no other children in the family. Both children and both parents were phenotypically Fy a - b+, reasonably common in Arab populations, so that any linkage to the Duffy blood group is neither supported nor refuted.

Human homologue for the mouse mutant disorganisation: does it exist?

We describe a newborn Arab male with defects similar to those seen in mice heterozygous for the mutant disorganisation (DS) gene. He had complete absence of the left lower limb including the left pelvic bone, hamartomas arising from the abdominal wall, a small penis, absent left half of the scrotal sac, absent left testicle, anterior displacement of the anus, and multiple vertebral defects. The similarity between the proband's anomalies and those found in affected heterozygotes for DS support the possibility of a human homologue of the DS gene.

Persistent Mullerian duct syndrome: report of two boys with associated crossed testicular ectopia.

Persistent Mullerian duct structures and crossed testicular ectopia were found in two phenotypically normal, unrelated males, with 46,XY karyotype, during routine herniorrhaphy. In each case, the vascular supply to the ectopic testis originated from the appropriate ipsilateral side. The clinical significance and genetic implications of this rare association are discussed.

Apparently nonmosaic trisomy 22: clinical report and review.

We report on apparently nonmosaic trisomy 22 in a liveborn girl with multiple congenital anomalies. The abnormalities were growth retardation; microcephaly; hypertelorism; epicanthic folds; anti-mongoloid slant; apparently low-set, malformed ears; highly arched, cleft palate; short webbed neck; and hypoplastic nails. The extra 22 was found to be of maternal origin by chromosome polymorphism.

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%.

Familial uterine hernia syndrome: report of an Arab family with four affected males.

We report an Arab Bedouin family including four males with uterine hernia syndrome. All had a male chromosome constitution and phenotype, inguinal herniae, cryptochidism, and persistence of Müllerian derivatives. Histopathological studies confirmed the presence of both testicular tissue and Müllerian derivatives. The presence of two affected brothers and two affected maternal uncles suggests X-linked inheritance. Autosomal recessive determination with male sex limitation is also a possibility based on parental consanguinity in one sibship.

New autosomal recessive faciodigitogenital syndrome.

Most pedigrees of Aarskog's faciodigitogenital syndrome have suggested X linked inheritance. However, sex influenced autosomal dominant inheritance is also a possibility in some families. We describe an Arab family of normal consanguineous parents with five children (three males and two females) with some features of Aarskog syndrome in addition to some unusual hair changes. The possibility that this family represents a distinct previously unrecognised faciodigitogenital syndrome with short stature and hair abnormalities is suggested and discussed.