Micronucleus assay as a biomarker for chromosome malsegregation in young mothers with Down syndrome children.

The aim of the present study is to test the susceptibility of chromosome 21 malsegregation in young mothers of Down syndrome children using combined micronucleus (MN) assay and FISH analysis. The present study included 62 Egyptian young mothers (age < 30 y) who were divided into 22 mothers of DS offspring and 40 age matched controls. All subjects were subjected to chromosomal analysis, micronucleus assay, and FISH analysis. High statistical significant difference was found between mothers of Down syndrome (MDS) and the controls in the MN percentage (P=0.034). Also there was high statistical significant difference between MDS and the controls in the percentage of positive malsegregation (P =0.0001). The specificity of combined MN% with FISH was 90%, while the sensitivity was 63.6%. Combined MN-FISH test is highly specific but moderately sensitive in assessing the risk of having children with DS in young mothers.

Oxidative Stress -a Phenotypic Hallmark of Fanconi Anemia and Down Syndrome: The Effect of Antioxidants.

BACKGROUND: Oxidative stress plays a major role in the pathogenesis of leukemia-prone diseases such as Fanconi anemia (FA) and Down syndrome (DS). AIM: To explore the oxidative stress state in children with DS and FA by estimating the levels of antioxidants (e.g., malondialdehyde [MDA], total antioxidant capacity, and superoxide dismutase [SOD] activity) and DNA damage, and to evaluate of the effect of antioxidant treatment on these patients. SUBJECTS AND METHODS: The study included 32 children clinically diagnosed with (15 patients) and FA (17 patients) in addition to 17 controls matched for age and sex. MDA, total antioxidant capacity, SOD activity, and DNA damage were measured. Antioxidants including Vitamin A, E, and C were given to the patients according to the recommended daily allowance for 6 months. Clinical follow-up and re-evaluation were conducted for all patients. Laboratory tests including complete blood count, karyotyping, DNA damage, and oxidative stress were re-evaluated. Statistical analysis was performed using statistical computer program Statistical Package for the Social Sciences version 14.0. RESULTS: Children with FA and DS had elevated levels of oxidative stress and more DNA damage than controls. Oxidative stress parameters and DNA damage improved in FA and DS patients after antioxidant administration. CONCLUSION: Early administration of antioxidants to FA and DS patients is recommended for slowing of the disease course with symptoms amelioration and improvement of general health.

The most encountered groups of genetic disorders in Giza Governorate, Egypt.

This study presents the prevalence, relative frequency, and analysis of genetic diseases/malformations in 73260 individuals. Cases included were ascertained from: Pediatric outpatient clinics of two governmental hospitals and two primary health care centers (PHCCs) in Giza Governorate; Neonatal intensive care unit (NICU) in the selected hospitals and Outpatients Human Genetics Clinics (NRC). 62819 persons visited the outpatients clinics of selected hospitals and PHCCs in Giza governorate. Out of these persons 731 cases (1.16%) proved to have known genetic disorders or malformations. 7755 neonates were delivered in the selected hospitals. Out of these neonates 666 newborns entered NICU and 3% (20 neonates) of them had genetic or congenital disorders. Also, 2686 patients were ascertained from the Human Genetics Clinics, NRC. The overall parental consanguinity rate among the 3417 diagnosed cases was 55%, ranging from 29.5-75%. The study showed a high prevalence of genetic/malformation disorders among Egyptians, with frequencies comparable to other Arab populations (Tab. 4, Ref. 25). Full Text (Free, PDF) www.bmj.sk.

Anorectal anomalies, diaphragmatic defect, cleft palate, lower lip pits, hypopigmentation and hypogammaglobulinemia A in Kabuki syndrome: a rare combination.

We report a rare combination of anomalies in an Egyptian girl with Kabuki syndrome (KS). The 26-month-old girl had imperforate anus with rectovestibular fistula, diaphragmatic defect, congenital heart defects, cleft palate, lower lip pits, hypopigmentation, seizures, hypogammaglobulinemia A, hyperlaxity of joints and premature breast development. This unique combination of anomalies, proposes to carefully investigate cases with KS patient in an attempt to determine their real frequency and in order to improve clinical management. Further, it raises a question about factors determining the variability in phenotypic expression among cases with KS. To our knowledge, this is the first case of KS to be reported from Egypt.

Distal 11q monosomy syndrome: a report of two Egyptian sibs with normal parental karyotypes confirmed by molecular cytogenetics.

Jacobsen syndrome is a rare disorder, caused by segmental monosomy for the distal end of the long arm of chromosome 11 with variable phenotypic expressivity. We report on the first male (6 years old) and female (3 years old) sibs with clinical and cytogenetics characterization of Jacobsen syndrome. Their karyotypes showed deletion 11q23.3-qter. Patients presented with growth and psychomotor retardation, facial dysmorphism, eye anomalies, and congenital heart disease (variable degrees of septal defect). Family history revealed a clinically similar brother, who died at 2 months old from cardiac anomalies in the form of single ventricle without being subjected to further investigations. Chromosomal analysis of the parents was normal. Karyotyping for the 2 patients and their parents was confirmed by fluorescence in situ hybridization analysis (FISH) using whole chromosome painting probes for 11 (WCP 11). Relevant investigations for both sibs showed mild thrombocytopenia with normal platelets morphology and striking periventricular demyelination on neuroimaging. Inguinal small testicles as well as focal epileptiform dysfunction were recorded in the male patient only. Abdominal ultrasound, hearing test, and DEXA scan were normal in both patients. Due to of the presence of apparently 3 affected offspring and normal parental karyotypes, an inherited predisposition was highly suspected. The large size of the distal deleted 11q segment in our patients support the recent hypothesis, that Jacobsen syndrome is a chromosomal deletion syndrome with genetic predisposition, due to expansion of p(CCG)n trinucleotide in the folate-sensitive fragile site FRA11B, at breakpoint 11q23.3. In conclusion, identification and further delineation of more similar patients will contribute to understanding the genetic basis of the 11q phenotype.

Elejalde syndrome: clinical and histopathological findings in an Egyptian male.

Elejalde syndrome is a rare disorder. An Egyptian male patient with Elejalde syndrome is presented. He had silvery hair since birth, generalized hypopigmentation, severe primary central nervous system dysfunction, and normal hematological and immunologic profiles. Magnetic resonance of the brain revealed prominent cerebellar atrophy with mild fronto-parietal cortical atrophic changes. Microscopic analysis of his hair showed melanin clumps irregularly distributed along the hair shafts, and a skin biopsy showed increased pigmentation in the basal melanocytes. The differential diagnosis of silvery hair disorders includes Elejalde syndrome, Griscelli and Chediak-Higashi syndromes. In the present report, we review the literature on Elejalde syndrome and discuss the differential diagnosis.

Mandibuloacral dysplasia: a report of two Egyptian cases.

Mandibuloacral dysplasia (MAD) is a rare disorder. Only 35 patients, coming from 22 families, have been reported worldwide. We report on two Egyptian unrelated girls with MAD. The first patient presented at the age of 5 years with acral defect and partial alopecia. The second patient presented at the age of 17 years with progressive micrognathia and loss of subcutaneous fat from the limbs. Physical examination detected the craniofacial, skeletal and cutaneous changes characteristic of MAD. Both patients were short with progeroid facies and loss of subcutaneous fat from the extremities, which fits lipodystrophy type A pattern. Radiological examination revealed delayed closure of cranial sutures, hypoplastic mandible, hypoplastic clavicles, and acroosteolysis. Both patients had normal glucose tolerance, but had fasting and post-prandial hyperinsulinemia, suggestive of insulin resistance. One patient had elevated serum triglycerides and low normal cholesterol levels, while the other patient had normal levels. Serum leptin was normal in both patients. We review the literature on mandibuloacral dysplasia and discuss the differential diagnosis.

Growth charts of Egyptian children with Down syndrome (0-36 months).

A study established growth and growth velocity curves for weight, length and head circumference in 350 Egyptian Down syndrome children (188 males and 162 females) from 0-36 months. Down syndrome children had poorer growth variables than normal healthy children through the first 3 years of life. Down syndrome children with associated congenital heart disease (90 cases) had significantly lower weight, especially in girls, compared with those without heart disease. In the first 2 years, growth velocity for weight and head circumference were higher in Down syndrome females than males, while growth velocity for length was higher in males. Down syndrome boys had slightly higher velocity of length than normal children in the first 3 years of life.

Growth charts of Egyptian children with Down syndrome [0-36 months]

A study established growth and growth velocity curves for weight, length and head circumference in 350 Egyptian Down syndrome children [188 males and 162 females] from 0-36 months. Down syndrome children had poorer growth variables than normal healthy children through the first 3 years of life. Down syndrome children with associated congenital heart disease [90 cases] had significantly lower weight, especially in girls, compared with those without heart disease. In the first 2 years, growth velocity for weight and head circumference were higher in Down syndrome females than males, while growth velocity for length was higher in males. Down syndrome boys had slightly higher velocity of length than normal children in the first 3 years of life

Evaluation of superoxide dismutase and glutathione peroxidase enzymes and their cofactors in Egyptian children with Down's syndrome.

The present work investigated the activity of Cu/Zn superoxide dismutase enzyme (SOD) in red blood cells and glutathione peroxidase enzyme (GPx) in whole blood by spectrophotometric methods. Plasma levels of the cofactors copper and zinc and whole-blood selenium were evaluated using atomic absorption spectrophotometer. The study included a population of 18 Down's syndrome (DS) patients with complete trisomy 21 (group 1), translocations (group 2), and mosaicism (group 3), and their 15 matched controls. The purpose of this work was to study the gene dosage effect of SOD and its consequence on GPx enzyme and the various cofactors, and to find out correlations with developmental fields. Our results showed that in the population with complete trisomy 21 and translocations, SOD and GPx activities were increased, whereas in cases with mosaicism, the enzymes activities were within normal limits. Plasma copper concentrations were increased, whereas whole-blood selenium concentrations were significantly decreased in the three DS groups. Plasma zinc levels were within normal in all patients. We concluded that changes in trace elements and enzyme activities were not related to age or sex. Also, there was no correlation between the enzyme levels and the developmental activities. Our results are useful tools for identifying nutritional status and guiding antioxidant intervention.

Mucopolysaccharidosis type I: clinical and biochemical study.

Of 1240 outpatients referred to the Human Genetics Clinic between 1997 and 1998, 248 (20%) had inborn errors of metabolism, 36 (14%) of which were diagnosed as mucopolysaccharidoses. Parental consanguinity was present in 82% of these patients. Deficiency of alpha-L-iduronidase (IDUA) enzyme in leukocytes and increased urinary mucopolysaccharides excretion were detected in 17 patients. The urinary spot test for glucosaminoglycans was inconclusive in 4 of the 17 cases. Results showed a correlation between the biochemical enzyme activity in leukocytes, the amount of excreted mucopolysaccharides and the subtype and course of mucopolysaccharidosis type I. We conclude that estimation of IDUA enzyme activity in leukocytes can differentiate between clinically overlapping cases of MPS I and MPS II and given the clinical manifestations of MPS I is a definitive and unequivocal method of diagnosis while the urinary spot test is inconclusive.

GAPO syndrome: first Egyptian case with ultrastructural changes in the gingiva.

We report on a 3-year-old boy with growth retardation, alopecia, pseudoanodontia, and optic atrophy. This is the 18th known and the first Egyptian case of GAPO syndrome. Electron microscopic examination of gingival biopsy showed excessive collagen fibres and endothelial vacuolisation, suggesting involvement of extracellular pathological collagenosis.

COFS syndrome with familial 1;16 translocation.

We report on an Egyptian girl with phenotypic abnormalities of cerebro-oculofacio-skeletal syndrome. She had microcephaly, bilateral congenital cataract, nystagmus, long ear pinnae, camptodactyly, prominent heels, coxa valga, kyphosis and flexure contracture of the elbows and knees. CT scan showed bilateral symmetrical intracranial calcifications. In addition, she had an apparently balanced translocation: 46,XX,t(1;16)(q23;q13) in all cells transmitted from a phenotypically normal mother with a similar balanced translocation mosaicism. We suggest that genes for COFS syndrome could be located on chromosome 1q23 or 16q13. We recommend chromosomal analysis and DNA studies in cases with COFS manifestations.

An epidemiological/genetic study of mental subnormality in Assiut Governorate, Egypt.

The aim of this investigation was to study the epidemiologic and genetic aspects of mental subnormality (MS) in Assiut Governorate, representing the Egyptian population. The sample comprised 3000 randomly selected subjects from three localities: one urban (Assiut City) and two adjacent rural villages. Age-matched controls were chosen for comparison. The Stanford-Binet test was administered to each individual. During history-taking special attention was paid to consanguinity and categorization on a genetic basis. The results revealed 116 cases with MS, showing an overall prevalence of 3.9%, which varied in the three locations: 3.4% in Assiut City, and 3.8% and 4.4% in the two rural locations. Clinico-genetic classification revealed the following: idiopathic MS 27.6%, MCA/MR syndromes 24.1%, primary CNS defect 12.9%, Martin-Bell syndrome 10.3%, inborn errors of metabolism 9.5%, tetratogenic and environmental causes 5.2%, MS and epilepsy 4.3%, chromosomal disorders 3.4% and MS associated with psychiatric disorder 2.6%. Parental consanguinity was found in 65% of the total sample, which emphasizes the role played by that factor in the etiology of mental subnormality in Egypt.

Economía y eficiencia en la formulación de una tasa

Distingue los tres factores que dominan la situación actual en la industria del abastecimiento de agua potable. Considera un modelo económico general, analizando la economía del agua y la fijación de precios y finalmente los cálculos de costos relacionados con un período de tiempo corto o largo. Se detiene en la teoría y práctica en la industria del abastecimiento de agua potable; aplicación de los principios económicos para la formulación de una tasa y escala propuesta de tasa de agua. Presenta una estructura de tarifas que se acomode a las necesidades y exigencias de la industria