Progressive osseous heteroplasia [POH]: an Egyptian patient

Progressive osseous heteroplasia is a rare genetic disorder characterized by cutaneous ossification during infancy and progressive ossification of subcutaneous and deep connective tissue including muscle and fascia during childhood. It is at the severe end of a spectrum of Guanine Nucleotide-binding protein, Alpha-Stimulating activity polypeptide [GNAS] associated ossification disorders that include osteoma cutis and Albright hereditary osteodystrophy. Here we describe a five year old boy with progressive ossification of skin and subcutaneous tissue and progressive limitation of movement of all joints. X-rays revealed extensive calcification of cutaneous and subcutaneous tissues involving nearly the whole body. As far as our knowledge, no cases have been reported before in the Middle East. Here we describe the first Egyptian child affected with this disorder

Triple A syndrome presenting with myopathy: an Egyptian patient

Triple A syndrome [Allgrove syndrome] is a rare, autosomal recessive disorder characterized by Adrenocorticotropic hormone resistant adrenal insufficiency, Alacrmia, Achalasia of the oesophageal cardia, progressive neurological degeneration and occasionally autonomic instability [making it 4A syndrome]. Reported neurological abnormalities included developmental delay, ataxia and polyneuropathy with sensory, motor and autonomic components, long-tract degeneration, parkinsonism and mild dementia. In this paper we report a 13 year old boy with Allgrove syndrome presenting with muscular weakness that was confirmed by EMG studies. To our knowledge, muscle disease in Allogrove syndrome was not reported before

Therapeutic approaches to genetic disorders

Although prevention is the ideal goal for genetic disorders, various types of therapeutic management are available. Such management approaches depend on the nature of the defect, how well it is understood at the genetic and biochemical levels and the practical feasibility of correction. In some conditions certain management is now tailored to the specific genotype. The patient being treated may be the fetus, the infant, the child or the adult. Treatment methods used in genetic disorders may involve surgical, cognitive/behavioral, pharmacologic, dietary, envairomental avoidance, transfusion, plasma exchange, enzyme, behavioral, cell, or gene therapy. Some have been developed on the basis of knowledge of the defect in the gene and its product, whereas others are empirical or aimed at controlling or mediating signs and symptoms without care

Maternal risk factors in young Egyptian mothers of down syndrome

We investigated the possible maternal risk factors that may increase the incidence of Down syndrome [DS] in young Egyptian mothers [younger than 35 years] especially methylene tetrahydrofolate reductase [MTHFR] enzyme C677T polymorphism. The study included 200 mothers of karyotypically ascertained non-disjunction DS attending Genetics clinic, Children's hospital, Ain Shams University [100 mothers were < 35 years and 100 mothers =/> 35 years]. 50 mothers of none-DS children served as a control group. For all cases, history was taken laying stress on: Parental ages at conception, maternal grandparent's ages at conception of mother, DS birth order, history of oral contraceptive use 6 months before conception, genital infection, vitamin supplementation and smoking or exposure to irradiation. MTHFR C677T mutational analysis was done to twenty DS mothers with ages

Inherited metabolic disorders causing cardiovascular diseases

In developed countries, cardiovascular disease is now the most common cause of death. Only recently, it has been recognized that a substantial number of inherited metabolic disorders contribute significantly to cardiovascular disability and death because of either a direct relationship between the inborn error and outcome or a genetic predisposition resulting from interrelation between gene variants and environmental factors. In this review, we summarized some of the more important genetic disorders affecting different components of the cardiovascular system

Updated listing of mutation map at the human phenylalanine locus among Egyptian population

Phenylketonuria is the most common inborn error of amino acid metabolism in Egypt with a relatively higher incidence of 1:7.500. Unrelated fifty-one PKU probands were selected from the database-records at the Medical Genetics Center, AinShams University-Cairo. We analyzed the DNA samples using polymerase chain reaction [PCR] combined with restriction enzyme assays, or allele specific oligonucleotide [ASO] testing and direct sequencing to detect 10 PAH gene mutations in exons 2, 3, 6, 7 and 11. We interestingly identified a novel missense CpG site R243P mutation. Moreover, three new known mutations L48S, delEX3 and Y277D unreeled in the Egyptian population. The ten detected mutations covered 58% representing 47 positive chromosomes. The most common mutation was represented by IVS10nt546 [10.8%], while the total missense mutations in our sample group account for the majority of mutations 40%. The high heterozygosity of the mutant PAH locus in Egypt suggests that multiple founder events would explain the presence of hyperphenylalaninemia in Egypt. Further studies will however be necessary to fully exploit the potential of PAH gene analysis to reconstruct the genetic history of PKU in Egypt in context with migrations among European and Mediterranean populations

Gallbladder disease in children with Down syndrome

Although gallbladder stones are known to be rare in childhood, a number of reports documented an increased prevalence of cholelithiasis and other gallbladder abnormalities in pediatrics patients with Down syndrome [DS]. The aim of our study was to find the frequency of gall bladder stones in children with DS and to investigate whether they have hypomotility of the gallbladder by ultrasonographically determined gallbladder volume and contraction index. The study included 20 children with DS diagnosed clinically and by cytogenetic analysis [study group] and 8 healthy children [control group]. Gallbladder diameters [length, width, and height], volumes and contraction index were measured in both groups by ultrasonography before and 30 minutes after a test meal. Fasting serum triglyceride and cholesterol levels were also determined. The median gallbladder fasting volume and contraction index were significantly lower in patients with DS compared to the control group. The median triglyceride level of the study group was higher than controls but the difference was statistically insignificant. Three patients with DS [15%] had asymptomatic gallbladder stones compared to none in the control group. In conclusion, incidence of gallbladder stones in DS children is high. Hypomotility of gallbladder [as evidenced by the lower contraction index] in DS could be considered a factor contributing to the high prevalence of gallstones in this group of patients

Femoral hypoplasia-unusual facies syndrome: femoral facial syndrome [FFS]: a recessive severe skeletal form

The femoral hypoplasia-unusual facies syndrome [FFS] is a very rare association of femoral and facial abnormalities. Maternal diabetes mellitus has been mainly involved as the causal agent. Autosomal dominant inheritance was described in few cases. We report a four-year old male with complete absence of both femora, not associated with other congenital anomalies except bilateral undescended testes

Methylation status of the KCNQ1OTand H19 genes in beckwith-wiedemann syndrome

The aim of this study was to assess the methylation status of the KCNQ1OT and H19 genes in patients with Beckwith-Wiedemann syndrome [BWS]. The study included three patients [two males and one female] diagnosed clinically as BWS. All patients showed hypomethylation of the KCNQ1OT gene and did not show abnormal methylation of the H19 gene. None of the three patients developed tumors in the follow up period. These results showed that the analysis of the methylation status of the KCNQ1OT and H19 gene is useful method in the diagnosis of BWS patients. Molecular diagnosis could be considered for defining the tumor risk in BWS patients

Dyggve-Melchior-Clausen syndrome: case report

Dyggve-Melchior- Clausen syndrome [DMC] is an autosomal recessive disorder characterized by mental retardation, short-spine dwarfism, and skeletal abnormalities, especially of the spine, hands and pelvis. Fifty eight cases have been reported in the literature. In this paper we report an Egyptian girl affected with this disease

Hypomelanosis of Ito associated with neuroblastoma

Hypomelanosis of Ito [HI] is a rare neurocutaneous disorder described for the first time in 1952 as incontinentia pigmenti achromians. The consistent feature of the disease is a characteristic cutaneous hypopigmentation areas following the lines of Blaschko, often associated with ocular, musculoskeletal and neurological abnormalities. In this paper, 1.5 year old child with HI and rapidly progressing neuroblastoma was described. Associated neuroblastoma was reported only once in the literature by Oguma et al., 1996

Cohen syndrome

We report two new cases of Cohen syndrome from two separate families. They have typical clinical features of non-progressive mental retardation, microcephaly, obesity and characteristic facial features