Estimating the birth prevalence and pregnancy outcomes of congenital malformations worldwide.

Congenital anomaly registries have two main surveillance aims: firstly to define baseline epidemiology of important congenital anomalies to facilitate programme, policy and resource planning, and secondly to identify clusters of cases and any other epidemiological changes that could give early warning of environmental or infectious hazards. However, setting up a sustainable registry and surveillance system is resource-intensive requiring national infrastructure for recording all cases and diagnostic facilities to identify those malformations that that are not externally visible. Consequently, not all countries have yet established robust surveillance systems. For these countries, methods are needed to generate estimates of prevalence of these disorders which can act as a starting point for assessing disease burden and service implications. Here, we describe how registry data from high-income settings can be used for generating reference rates that can be used as provisional estimates for countries with little or no observational data on non-syndromic congenital malformations.

Experience of a multidisciplinary task force with exome sequencing for Mendelian disorders.

BACKGROUND: In order to optimally integrate the use of high-throughput sequencing (HTS) as a tool in clinical diagnostics of likely monogenic disorders, we have created a multidisciplinary "Genome Clinic Task Force" at the University Hospitals of Geneva, which is composed of clinical and molecular geneticists, bioinformaticians, technicians, bioethicists, and a coordinator. METHODS AND RESULTS: We have implemented whole exome sequencing (WES) with subsequent targeted bioinformatics analysis of gene lists for specific disorders. Clinical cases of heterogeneous Mendelian disorders that could potentially benefit from HTS are presented and discussed during the sessions of the task force. Debate concerning the interpretation of identified variants and the content of the final report constitutes a major part of the task force's work. Furthermore, issues related to bioethics, genetic counseling, quality control, and reimbursement are also addressed. CONCLUSIONS: This multidisciplinary task force has enabled us to create a platform for regular exchanges between all involved experts in order to deal with the multiple complex issues related to HTS in clinical practice and to continuously improve the diagnostic use of HTS. In addition, this task force was instrumental to formally approve the reimbursement of HTS for molecular diagnosis of Mendelian disorders in Switzerland.

Prevalence of consanguineous marriages in South Sinai, Egypt.

A total of 3961 married couples from six major geographical areas representing the South Sinai governorates in Egypt were studied to assess the rate of consanguineous marriage. The population of six selected areas (St Catherines, Nuweiba, Abu Rudeis, Ras Sudr, El Tor and Abu Zenima) were subdivided into Bedouin, urban and mixed populations. A questionnaire-based interview was conducted showing that the consanguinity rate in this region is 37.5%, with the highest rate recorded in Abu Rudeis (52.3%) and lowest rate in Nuweiba (24.1%). Consanguinity was significantly higher among the Bedouin population compared with the urban population in Abu Rudeis, Ras Sudr, El Tor and Abu Zenima, while in St Catherines and Nuweiba there was no statistically significant difference. Among consanguineous couples, 5%, 60% and 35% were double first cousins, first cousins and second cousins respectively. The mean inbreeding coefficient α of the studied population was 0.01845.

Sanjad Sakati syndrome: a case series from Jordan.

Sanjad Sakati syndrome is a rare autosomal recessive disorder that has been described in Arabs. We report 8 patients from 7 Jordanian families, 6 of whom underwent genetic testing and were found to have a 12 bp (155-166 del) deletion within the tubulin-specific chaperone E (TBCE gene) in exon 3 at 1q42-43. All patients had severe growth retardation, distinct phenotypic features and hypoparathyroidism. Parental consanguinity was recorded in all families. This is the first genetically proven case series of Sanjad Sakati syndrome in Jordan.

Sanjad Sakati syndrome: a case series from Jordan

Sanjad Sakati syndrome is a rare autosomal recessive disorder that has been described in Arabs. We report 8 patients from 7 Jordanian families, 6 of whom underwent genetic testing and were found to have a 12 bp [155-166 del] deletion within the tubulin-specific chaperone E [TBCE gene] in exon 3 at lq42-43. All patients had severe growth retardation, distinct phenotypic features and hypoparathyroidism. Parental consanguinity was recorded in all families. This is the first genetically proven case series of Sanjad Sakati syndrome in Jordan

Genetic clinics in arab communities: meeting individual, family and community needs.

Arab societies are characterized by a wide range of family and social structures, religious and legal conventions, and highly variable economic resources. As might be expected under these circumstances, genetic services cannot readily be devised, delivered, and assessed according to a single model. However, in general terms, the provision of genetic services in Arab communities at all population levels is still inadequate given the prevalence and burden of genetic diseases. Improving this situation calls for major educational efforts that include increasing the genetic literacy of the general public, comprehensive courses and campaigns to familiarize primary health care workers with counseling needs and skills and with referral guidelines for high-risk families, updating medical, nursing, and paramedical curricula to incorporate information on community genetics, and training clinical and laboratory genetic specialists to meet the short- and long-term goals of genetic disease prevention and management.

Congenital pseudoarthrosis associated with venous malformation.

Congenital pseudoarthrosis is a pathologic entity that may be isolated, or may be associated with neurofibromatosis. We report the case of a 3-year-old female with congenital pseudoarthrosis involving the right tibia and fibula. Magnetic resonance imaging (MRI) and complementary magnetic resonance angiogram (MRA) revealed a lobulated mass with vivid enhancement, which led to the diagnosis of venous malformation. This is the first report of congenital pseudoarthrosis caused by the presence of a vascular malformation.

Consanguineous marriages in Jordan: why is the rate changing with time?

The objective of this study was to explore the secular trend in consanguinity in Jordan and the subtypes of consanguineous marriages that may be undergoing a change. A total of 1032 individuals attending a diabetic clinic in Amman were interviewed. The questionnaire provided information on consanguinity status and date of marriage among three generations: the persons interviewed, their parents, parents of their spouses and their offspring. Data on consanguinity status among 5401 marriages was obtained. Generations were named generation 1 for marriages contracted before 1950, generation 2 for marriages contracted between 1950 and 1979, and generation 3 for marriages contracted after 1980. For generations 1, 2, and 3, first-cousin marriages constituted 20.2, 28.5 and 19.5% of all marriages, respectively, while the subtype of paternal parallel first-cousin marriages constituted 75.6, 60.3 and 43.3% of all first-cousin marriages, respectively. The offspring of first-cousin parents were significantly more prone to marry their relatives than the offspring of non-consanguineous parents, with rates of first-cousin marriages among offspring of first-cousin parents and non-related parents constituting 25.3 and 17.1% of all marriages, respectively. For generations 1, 2 and 3, the average coefficient of inbreeding was 0.0135, 0.02 and 0.0142, respectively. In conclusion, first-cousin marriage rate among a representative population from Amman showed a significant decline among marriages contracted after 1980 compared to marriages contracted between 1950 and 1979, but not to marriages contracted before 1950. The proportion of paternal parallel first cousins among first-cousin marriages showed a steady decline from one generation to the next.

Precocious puberty at an endocrine centre in Jordan.

BACKGROUND: Data from developed countries about precocious puberty are abundant; data from developing countries are limited. Causes are different, and diagnostic and treatment possibilities are very expensive. The present study aimed to display the spectrum of initial presentation and aetiology among children with precocious puberty and to assess any association between th e clinical features and the underlying cause of the condition. PATIENTS AND METHOD: Forty-three girls and seven boys with precocious puberty were diagnosed at the Endocrine Clinic of Jordan University Hospital and at The National Center for Diabetes, Endocrinology and Genetics, Amman, Jordan, between the 1984 and 2003. RESULTS: Mean age for the girls with precocious puberty was 4.1 years +/- 2.5 SD and for the boys was 2.4 years +/- 1.9 SD. Among the girls, 21% presented with breast development only, 9% with pubic hair appearance only and 70% with multiple signs. All the boys presented with pubic hair appearance and enlarged genitalia. Organic causes for precocious puberty were detected in 42% of the girls and in all the boys. Idiopathic precocious puberty was more common among the girls presenting with breast development only (89%) compared with those presenting with multiple presenting signs (50%), and also was more common among girls presenting between 6 and 8 years (82%) than among those presenting < 6 years of age (42%). Congenital adrenal hyperplasia was diagnosed in four boys and four girls, and hypothyroidism in three girls. CONCLUSION: Precocious puberty in the girls was usually of idiopathic origin when it presented with breast development only and at age older than 6 years. Congenital adrenal hyperplasia and hypothyroidism could represent important causes for precocious puberty in our community.

Treatment of cutaneous leishmaniasis by direct current electrotherapy: the Baghdadin device.

Electrical stimulation has been used as a mode of therapy for a number of clinical conditions. However, it has not been used for the treatment of cutaneous leishmaniasis (CL). For this purpose, we designed the "Baghdadin device". A total of 146 lesions of acute CL in 54 patients were treated by this device. Twenty-one lesions in the same patients were left untreated as controls. In addition, 36 lesions in 15 patients were treated with intralesional sodium stibogluconate. Treatment by the Baghdadin device consisted of weekly sessions of 10 minutes of direct current electrical stimulation. The intensity of the direct current ranged between 5 and 15 milliamperes, and the voltage was kept below 40 volts. Of the 146 lesions, 135 (92.5%) showed total clearance or marked improvement in 4-6 weeks time. Approximately 67% of the lesions needed only one or two sessions. Scarring was not observed after resolution. None of the untreated lesions showed any signs of improvement in 6 weeks. Of the lesions treated with sodium stibogluconate, 32 lesions (88.9%) showed total clearance or marked improvement, which was not significantly different from the results with the Baghdadin device.

Hereditary disorders in the Eastern Mediterranean Region.

Hereditary diseases and congenital malformations have been reported to affect 2-5% of all live births. Available evidence suggests that genetic disorders are equally important also in countries of the Eastern Mediterranean Region. Considerable achievements have been made over the last two decades in controlling communicable diseases in the region. Concurrently, there has been a mounting awareness of the increasing importance of hereditary disorders. Certain genetically determined diseases such as the haemoglobinopathies and enzymopathies are extremely common in the region and the need to initiate public health measures for their control is increasingly being recognized. The following factors may contribute to the elevated prevalence of genetically determined disorders: the high consanguinity rates; the high frequency of haemoglobinopathies and glucose-6-phosphate dehydrogenase deficiency; the trend of continuing to bear children up to menopause; the general lack of public awareness about genetic diseases; and the dearth of genetic services in the region. These and some other related issues are discussed in detail in this review article.

Sister chromatid exchange frequencies in a group of individuals with unfavorable reproductive health.

Sister chromatid exchange (SCE) frequencies and other cytogenetic parameters were investigated in peripheral blood lymphocytes from 92 subjects comprising 44 parents of malformed offspring or repeated fetal wastage (Group I) and 48 controls, age and sex matched, having normal reproductive health (Group II). The karyotypes were normal and the mean mitotic indices were comparable in both groups. The mean frequency of SCE per metaphase in Group I (8.67 +/- 0.32) was significantly higher than the mean for group II (6.65 +/- 0.16), and the cellular replicative index in Group I (1.78 +/- 0.04) was significantly different from that of Group II (1.66 +/- 0.03). The results are discussed in the light of the present understanding of the etiology and mechanism of production of sister chromatid exchanges.

Consanguinity and the genetic control of Down syndrome.

Eighty-three infants and children with a professional diagnosis of Down syndrome were studied cytogenetically. The results showed that 81.9% of them were trisomy 21 and 18.1% were the 46/47 + G type of mosaic. All cases were distributed according to parental consanguinity. The results showed that 77.9%, 16.2% and 5.9% of the trisomy 21 cases, and 53.3%, 26.7% and 20.0% of the mosaic cases were from non-consanguineous, first-cousin and second-cousin marriages, respectively. By combining all the cases, these percentages were 73.5%, 18.1% and 8.4%, respectively. Considering the high rate of inbreeding in Iraq (inbreeding coefficient = 0.0225) and using various statistical comparisons, these results revealed the lack of evidence for genetical control of non-disjunction in man.

Consanguinity and reproductive health in Iraq.

This study investigated the consanguinity rate of 233 families with severely disturbed reproductive health, and compared it to that of 227 families with normal (moderate) levels of reproductive wastage and to that of 155 families with no reproductive disturbance. The results showed that the inbreeding coefficients of the three groups of families were 0.0358, 0.0241 and 0.0208, respectively. Furthermore, the rate of congenital malformations was found to be highly correlated with the consanguinity rate of these families.

Chromosome aberrations in workers at a tannery in Iraq.

Blood samples were collected from 17 healthy chromium-exposed workers at a tanning plant near Baghdad city and 13 controls matched for age, period of service and social background. For each individual more than 100 lymphocyte metaphases were examined. The results showed no significant differences in the per cell frequencies of chromatid and isochromatid gaps, single chromatid breaks, various chromosome-type aberrations and all aberrations combined. However, smoking workers exhibited statistically higher frequency of chromosome-type aberrations than non-smoking workers and smoking controls.