Variability of cardiac and limb involvement in the Holt-Oram syndrome

Holt-Oram Syndrome [HOS] is a rare genetic disorder characterized by variable degrees of malformations of the upper limbs and/or congenital heart disease. We present here nine affected cases, eight in three families and one sporadic case who exhibited variable features of the syndrome and showed a wide spectrum of abnormalities involving the skeletal system, specially the upper limbs, and cardiovascular system. This is probably the second report of Holt-Oram syndrome in Egyptians. The first report was in 1970 by Temtamy and El-Mazny[1]. The etiology of HOS is autosomal dominant disorder mostly due to mutation in TBX5, a box containing transcription factor. It has been suggested that SALL4 mutations might cause HOS. It is important to study the occurrence and spectrum of severity of HOS particularly in relation to the types of mutations affecting TBX5 and SALL4

genetic epidemiological study of malformations at birth in Egypt

A total of 3000 consecutive neonates delivered in a maternity hospital in Giza, Egypt, were subjected to full clinical and genetic evaluation. Social data included parental consanguinity and social class. The prevalence of malformations in the 3000 hospital live births and stillbirths was 3.17%. Malformed neonates [95] were classified into 13 groups according to the system affected using World Health Organization classification of congenital malformations. The most common anomalies were: central nervous system [29.5%], musculoskeletal system [20.0%] and genetic syndromes [13.7%]. Parental consanguinity was found in 31.79% of all cases and in 55.0% of malformed cases, thus illustrating the deleterious effects of consanguinity

Genetic studies of hepatomegaly with fatty liver change in Egyptian children

The present work included 18 cases with liver diseases suspected to have genetic etiology. These were detected out of 33 cases with hepatomegaly and significant fatty liver change. For each case, complete clinical and genetic evaluation, specific investigations, and liver biopsy for histopathological studies were done. The following results were obtained: 8 cases had Gaucher disease, 8 cases had glycogen storage disease and 2 cases had Niemann-Pick disease. Positive consanguinity was found in 89% of the studied cases and positive family history was present in 55% of the studied cases. Genetic etiology is responsible for 54.5% of cases with fatty liver change. Autosomal recessive inheritance was suggested in all genetically determined cases. It is concluded that the morphological picture combined with clinical examination and pedigree studies may be sufficiently distinctive to indicate the etiological diagnosis

Orodental, ear and eye anomalies in Egyptian Brachmann de Lange syndrome cases

The Brachmann de Lange syndrome [BDLS], first described in its full clinical presentation by Brachmann [1916] and Cornelia de Lange [1933] is a multi-system syndrome involving congenital malformations, growth retardation and neurodevelopmental delay. We describe here twelve Egyptian cases with this syndrome with emphasis on the orodental, ear and eye abnormalities and their relation to the severity of expression of the disorder. The orodental anomalies were high arched palate, long philtrum micrognathia, macrostomia, hypoplasia of upper anterior teeth, fissured tongue and macroglossia. Ear malformations were low-set large ears. Otoscopy revealed normal drum appearance. Audiogram revealed conductive, sensorineural or mixed hearing loss. Ocular manifestations were nystagmus, convergent squint, enophthalmos, myopia 8 blue scleca. The study emphasizes certain eye, ear and orodentat anomalies as diagnostic features of the BDLS which correlate with the severity of expression of the syndrome. None of the cases had chromosomal aberrations and the parental consanguinity rate was not increased thus supporting dominant mutations or minor chromosomal etiology

Some biochemical screening tests of metabolic disorders in Egyptian children suffering mental retardation

The present study deals with investigation of the biochemical abnormality and the metabolic disorders which may be the cause or contribute significantly to the cause of mental retardation [MR]. The study included 203 mentally retarded children who were subjected to qualitative chemical tests on urine for the detection of certain defects in amino acid and carbohydrate metabolism. Thin layer chromatographic detection of specific amino acids in plasma and urine, and the quantitative determination of urea, creatinine, ammonia and uric acid in plasma, argininosuccinase and argininase enzyme activities in erythrocytes; mucopolysaccharides and creatinine in urine were also investigated. It was found that in 92 patient, mental retardation is accompanied by metabolic disorders. These comprise disorders in amino acid transport [10.6%] urea cycle abnormalities [17.4%], generalized amino acid urea [10.8%], miscellaneous aminoacidopathies [25%] and defects in carbohydrate metabolism [26.1%]. The plasma levels of urea, uric acid and creatinine in patients with disorders in aminoacid transport were unchanged indicating normal kidney function. Patients with urea cycle abnormalities showed deficiency in different enzymes controlling urea formation with elevation in plasma ammonia and decrease in plasma urea. Patient with carbohydrate metabolism disorders showed increased urinary mucopolysaccharides. These metabolic disorders were discussed on the basis of the findings obtained and the genetic defect that led to the respective metabolic disorder. According to results of this work, it is highly recommended to carry out genetic counselling in calculating the possibilities for recurrence risk of hereditary disorders and in detecting any metabolic abnormality to prevent the onset of mental retardation. Early detection of these cases and evaluation of specific treatment will be valuable for the management of these cases

Chromosomal studies on laboratory rats [Rattus Norvegicus] exposed to an organic solvent [cyclohexanone]

Cyclohexanone, an aromatic hydrocarbon, was tested for its ability to induce chromosomal abnormalities in male laboratory rats, [Rattus norvegicus], 6, 24 and 48 hours after subcutaneous injection of three doses: 0.1, 0.5 and 1.0 g/kg. The effect of these treatments was scored cytologically in metaphase plates of bone marrow cells. The results showed that the compound was effective in the induction of chromosomal aberrations at all doses and time intervals. The induced abnormalities increased with dose and decreased with time. Qualitatively, they consisted of chromatid gaps and breaks, centric fusions, centrometric attenuation, chromatid exchanges and polypioidy. It was concluded that cyclohexanone could exert harmful effects on mammalian chromosomes, and might accordingly be genetically hazardous to man