Molecular characterization of X chromosome fragility in idiopathic mental retardation

Background: Fragile X syndrome [FXS] is the most common form of inherited mental retardation. Frequency of fragile X syndrome among male siblings and relatives of mentally retarded patients is relatively high. Cytogenetic diagnosis of FXS is unreliable since it is ineffective for the diagnosis of premutated males or females. Proper molecular diagnosis is a pre-requisite for providing proper counseling advice

Subjects and methods: Sixty-four males with idiopathic mental retardation, ranging in age from 4.2 to 19 years [10.92+/- 4.00] were clinically pre-selected, based on scoring protocol comprising eight features of the syndrome, before molecular testing. A rapid polymerase chain reactionbased screening was applied for detection of expanded FMR1 alleles. Samples that did not yield the normal band lengths were subjected to a second PCR screen. The secondary screen utilizes a chimeric primer demonstrating the presence or absence of an expanded allele

Results: Amplification of FMRI gene by PCR of tested patients revealed that 8 cases [12.5%] have full mutation and 6 cases [9.4%] have premutation. A wide range of Fra X-scoring ranging from 1 to 7 features was detected in examined cases. Significant clinical features included large prominent ears, hyperextensibility of joints and macroorchidism in post pubertal males

Conclusions: A simplified checklist of fragile X should be used for patients with idiopathic MR and those patients above score 3 should be tested for FXS. The diagnostic assay may be used as a screening method for fragile X syndrome being rapid and cost effective compared to other techniques. In addition, screening of all relatives of proven patients should be performed to detect clinically unidentified cases for provision of proper counseling and optimal management of detected cases

Cardiological assessment of a cohort of Egyptian patients with osteogenesis imperfecta type III

Background: Osteogenesis imperfecta is a genetic disorder of bones, which has different types. Type III is characterized by recurrent fractures, progressive bone deformities. Cardiac manifestation is one of the important extraskeletal manifestations

Aim of the study: To asses the ECHO cardiographic findings in Egyptian osteogenesis imperfecta patients type III [OI III]. Patients and methods: This retrospective study included 35 OI III patients. Their age ranged from 2 months to 18 years with a mean of 6.34 +/- 4.85. Standard echocardiography was performed, and heart valves were examined. The dimensions of the left ventricle, and ejection fraction were measured

Results: Abnormal ECHO findings were found in 8 patients [22.9%]. Atrial septal defect [ASD], and patent ductus arteriosus [PDA] were the commonest cardiac findings with 5.7% each. Trivial tricuspid regurge was found in 9 patients, this was considered normal finding. There was no significant difference in ECHO findings between males and females with OI III

Conclusion and recommendation: The presence of cardiac abnormalities is documented in OI patients whether congenital or valvular, and so ECHO cardiography should be routine in all patients with OI

Chromosomal abnormalities and autism

Background: Autism is a neurodevelopmental disorder characterized by clinical, etiologic and genetic heterogeneity. Many surveys revealed cytogenetically visible chromosomal abnormalities in 7.4% of autistic patients documented as well as several submicroscopic variants. This study had been conducted to identify some aspects that might be involved in the pathogenesis of autism which is necessary for offering proper genetic counseling to families of autistic patients and their role in the prenatal diagnosis of autism

Methods: This cross sectional study was conducted at the Child Psychiatry Clinic, Pediatric Hospital, Ain Shams University on 30 autistic patients who were subjected to the following tools: Confirmation of diagnosis using DSM-IV-TR criteria, IQ assessment using Stanford-Binet intelligence scale and assessment of severity of autistic symptoms using childhood autism rating scale [CARS]. Full clinical examination, neurological examination, EEG, audiological assessment were also done. High resolution karyotyping was done for detection of numerical or structural chromosomal abnormalities as deletion, duplication, translocation of chromosomes

Results: All the results of cytogenetic analysis were normal with no detectable numerical or structural chromosomal abnormalities. Males are affected more than females, only one case had history of drug intake [progestin], two cases had history of anti-D injection and two cases had history of diabetes mellitus during pregnancy. Four cases had history of respiratory distress and seven cases had history of jaundice. Two cases had history of generalized tonic clonic convulsion and four cases had history of EEG abnormalities. Fifteen cases of our autistic patients had mild mental retardation and six cases had moderate mental retardation

Conclusion: Chromosomal abnormalities were not detected in the studied autistic children, and so the relation between the genetics and autism still needs further work up with different study methods and techniques

Selective screening in neonates suspected to have inborn errors of metabolism

Inborn errors of metabolism [IEM] have a high morbidity and mortality in neonates. Unfortunately, there is no nationwide neonatal screen in Egypt, so several cases may be missed. The aim of this work was to detect the prevalence of IEM among neonates with suspected IEM, and to diagnose IEM as early as possible in order to minimize morbidity and mortality in high risk neonates. This prospective study included 40 neonates admitted to the Elmahalla General Governmental Hospital Neonatal Intensive Care Unit [NICU] with sepsis like symptoms [lethargy, hypoactivity, poor suckling, and poor crying], convulsions, persistent metabolic acidosis, persistent vomiting, or previous sib death of unidentified cause [neonates with suspected IEM]. All included patients were subjected to detailed full history, through clinical examination, laboratory investigations, and metabolic screening by tandem mass spectrometry [MS/MS]. Other investigations for IEM including lactate, ammonia, and galactose 1 phosphate levels in the blood, as well as organic acids in urine were done according to each case. 13 patients [32.5%] were diagnosed as having IEM, 7 of them [53.8%] had urea cycle defect, 2 [15.4%] had maple syrup urine disease, while methylmalonic acidemia, fatty acid oxidation defect, mitochondrial disease, and galactosemia were diagnosed in one patient each [7.7%]. Out of these patients, 12 patients [30%] were discharged from NICU after therapy, and one patient [2.5%] died [the one who had mitochondrial disease]. Two patients were diagnosed as diseases other than IEM, one had hyperinsulinism and another one had congenital myopathy, while 2 patients were proved to be normal. Five patients [12.5%] were suspected to have IEM [tyrosinemia, mitochondrial disease, organic academia] 4 of them died before final diagnosis, and one transferred to another NICU. There was a significant difference between diagnosed and undiagnosed patients as regards history of sibling death]p = 0.012], plasma ammonia level [p = 0.002], and discharge from NTCU [p = 0.000]. Conclusion: IEM represent a high percent [32.5%] of neonates who had sepsis like symptoms, and when diagnosed, patients showed marked improvement after therapy. IEM should be considered in differential diagnosis of the sick neonates, and investigations, and management should be started rapidly to decrease morbidity, and mortality till nationwide screen for IEM is applied in Egypt

Trichorhinophalangeal syndrome II, expanding the clinical spectrum

We report a 4.5 year old Egyptian male child, fourth in the order of birth of healthy remote consanguineous parents. He has typical facial as well as skeletal features of Trichorhinopha-langeal syndrome [TRPS] II. The facial features included bilateral downward slanting palpebral fissures, bulbous nose, long filtrum, retromicrognathia, sparse hair in the scalp and thick eyebrows. The skeletal features included retarded bone age, cone shaped epiphyses of the phalanges and multiple exostoses. The patient has also growth retardation, moderate mental retardation and hyperlaxity of the right knee joint. However our patient has some features not reported in TRPS II patients. These included bilateral partial ptosis, long eye lashes, preauricular skin tag, short 2nd right finger, short metacarpals of both thumbs. So we have to expand the clinical spectrum. Karyotype demonstrated 46,XY,del 8[q23.3-q24.1]

Demographic and clinical features of glutaric acidemia type 1; a high frequency among isolates in Upper Egypt

Glutaric acidemia type 1 [GA1] was thought to be a rare disorder in Arab countries. Recently, a relatively large number of patients with GA1 have been detected in Egypt. The aim of this work was to: [1] find out the commonest clinical characteristics of the disease among Egyptians presenting with GA1; [2] delineate the demographic factors that may lead to a high prevalence of GA1 among Egyptians; [3] Recommend the most suitable strategy to screen for the disease. The study included all patients with GA1 who presented at The Genetics Unit, Ain Shams University Hospital [GUASH] during the last three years. The information about patients with GA1 including the epidemiological and clinical data was obtained retrospectively from patients' files. The authors surveyed data of 26 patients in 23 families who were personally examined and the diagnosis was confirmed by laboratory data. The mean age of onset of symptoms was 5.8 +/- 2.2 months: the mean delay in establishing the diagnosis was 11.73 +/- 13.97 months. At the onset of symptoms, macrocephaly [85%] was the commonest feature of GAI followed by dystonia [69%], and persistent convulsions [50%]. Onset of symptoms occurred during an acute febrile illness in 68% of patients, which was associated with the worst forms of dystonia [X2 = 12.5, p =0.14]. The frequency of affected Christian families among all affected families was 43%, which is significantly higher than that expected of the Christian minority in Egypt [6-15%]. There has been no significant increase in consanguinity among those Christian families [F = 0.014204] pointing to a high gene frequency of GA1 in isolated areas in Upper Egypt. In the absence of mass newborn screening program, continuous Health Education program should be implemented to promote detection of early signs of GA1 such as macro-cephaly before the occurrence of acute crisis of encephalopathy especially in families with history of similar patients. We recommend that a nationwide program of extended tandem mass screening should cover all newborns in Egypt to promote early detection of patients with GA1 and to avoid the severe consequences of the delay in diagnosis

Bilateral absence of fifth ray in feet, cleft palate, malformed ears, and corneal opacity in a patient with Miller syndrome

Miller syndrome is one of the acrofacial dysostosis syndromes, which are characterized by malformations of the craniofacial region and limbs. A 26 month old male child, the product of healthy nonconsanguineous parents has many typical features of Miller syndrome. He has cleft lip and palate, malar hypoplasia, left crumpled cup shaped ear, and prominent nose together with the absence of the fifth ray in feet [postaxial] and fixation of interphalangeal joints of both thumbs [preaxial]. However the limb affection is bilateral and symmetrical against what is usually reported [bilateral with more affection of one side] and the micrognathia is very mild. Our patient has also bilateral corneal opacities as well as underdeveloped external genitals. There is phenotypic variability in Miller syndrome, and our patient may represent a new distinct subgroup in postaxial acrofacial dysostosis

Intrafamilial variability in Simpson-Golabi-Behmel syndrome with bilateral posterior ear lobule creases

We report a family having two male sibs with Simpson-Golabi-Behmel syndrome [SGBS]. Both have many typical features of the syndrome. These features included macrocephaly, macroglossia, post axial polydactyl of the left hand, bilateral low insertion of the thumb, multiple accessory nipples, hepatomegaly, and congenital heart. The patients have bilateral anterior helical ear pits, and characteristic posterior ear lobule creases. The older one has severe mental retardation and died at the age of 13 months with bronchopneumonia, and the younger one is 7 months old with normal mentality. The mother looks broad, stocky, and tall

Bilateral iris, choroid, optic nerve colobomas and retinal detachment in an Egyptian patient with mild Baraitser-Winter syndrome

Baraitser-Winter syndrome [BRWS] is a malformation syndrome, characterized by facial dysmorphism, ocular colobomata, pachygyria, and intellectual defects. A 3.5 year old female child with BRWS has bilateral congenital ptosis, microcor-nea, iris, choroid, and optic nerve coloboma, retinal detachment, and mental retardation. She has also frontal bossing, prominent forehead, thick eyebrows, transverse slanting, hypertelorism, wide palpebral fissures, and nystagmus. The nose is broad, and bulbous with wide nares, and broad nasal tip. She has also low set posteriorly rotated ears, full cheeks, long philtrum, large mouth [macrostomia], gum hypertrophy, decayed teeth, high arched palate, pointed chin, short neck, low posterior hair line, partial left simian crease, and short fingers. MRI brain shows frontal poly-microgyria. This patient represents a mild case of Baraitser-Winter syndrome

Cornelia-de Lange syndrome in an Egyptian infant with unusual bone deformities

We report a 4 month old female infant with the typical features of Cornelia-de Lange syndrome. What was striking in our patient was the presence of skeletal anomalies not reported previously. These included arachriodactly of both fingers and toes, flexion of thumbs at metacarpoph alengeal joints, bilateral short big toes, angulation of the lower part of the bones of right forearm and both legs with multiple skin folds. Also biochemical and X-ray evidence of rickets was detected mostly due to malnutrition and failure to thrive. The patient died at the age of 5 months with bron chopneumonia and gastroenteritis

Changes of amino acid neurotransmitter concentrations in striatum and thalamus induced by exposure of young and adult rats to electromagnetic radiation

The rapid rise in the use of mobile communications has raised the questions about the health issues. The head and the brain are usually the most exposed targets in mobile phone users. Over the last decade, exposure to high frequency electromagnetic radiation [EMR] has been found to induce deficits in rodents in spatial memory tasks. In addition, radiofrequency radiation has measurable effects on human cognitive performance. The aim of the present study was to investigate the effects of 900MHz EMR on some amino acid neurotransmitters [glutamic acid, glutamine, GABA, glycine and taurine] to measure their significant variations in the thalamus and striatum of adult and young rats

In the present study, both adult and young rats were exposed to EMR at a frequency of 900MHz, a power density of 0.02mW/Cm[2] and an average specific absorption rate of 1.165 W/Kg for one hour daily. Both the exposed and control rats were decapitated after 1h, 1,2 and 4 months of daily exposure to EMR and another group was decapitated after 1 months of stopping the exposure that extended daily for 4 months. Most of the excitatory and inhibitory amino acid meurotransmitters in the thalamus and straitum of the two ages showed significant increase after 1h of a single exposure. This increase persisted in the two areas of the adult animals only throughout the three time intervals [1, 2 and 4 months of daily exposure]. However, in the young rats this increase was normalized after 1 and 2 months and reappeared after 4 months. The most prominent effect recorded after stopping exposure was a significant increase in the striatal excitatory amino acid neurotransmitters of adult rats and a decrease in striatal GABA in young animals. The present reported data cannot exclude the possibility of the microwave-induced biological effects on the brain at a power level and frequency related to mobile communication. It may be concluded that the alteration in the amino acid neurotransmitters may provide one of the mechanisms underlying the memory and cognitive disorders induced by mobile phone radiation

Effect of exposure to electromagnetic radiation from the mobile phone on acetylcholinesterase activity in the hippocampus and striatum of young and adult male rats

Acetylcholine is an established neurotransmitter in the transmission of signals in many of brain neurons. A decrease in the activity of cholinergic systems has been implicated to underlie the memory disturbances resulting from electromagnetic radiation [EMR]. The present study shows clearly that EMR from mobile phone [at a frequency of 900MHz, a power density of 0.02mW/cm[2] and an average specific absorption rate of 1.165W/kg] had an adverse effect on acetylcholinesterase [AchE] activity, the enzyme specific for the functioning of acetylcholine. The exposure of young male rats to the previous EMR for one hour caused a significant increase in AchE activity in the hippocampus, but not in the striatum, whereas the prolonged exposure for one month and four months [1 h daily] induced a significant increase in the enzyme activity in both areas. Both acute [I h] and prolonged [1 and 4 months, 1h daily] exposure to EMR produced significant increases in AchE activity in both hippocampus and striatum of adult male rats. The increase in the enzyme activity continued also after stopping EMR exposure for one month. The implication of these changes to the brain functions of the cholinergic system in both areas is discussed