Biomedical subjects

S A Temtamy

Publications and source records attributed to S A Temtamy.

At least 19 recordsLinked to original sources

PubMed2006

Roberts syndrome: study of 4 new Rgyptian cases with comparison of clinical and cytogenetic findings.

Roberts syndrome is a rare autosomal recessive genetic disorder (MIM 268300). It is characterized by pre and postnatal growth retardation, severe shortening of limbs with radial defects, oligodactyly and characteristic facial features. The present study reports 4 new cases of Roberts syndrome from 3 families presenting variable phenotypes. Patients were thoroughly investigated clinically and cytogenetically. By reviewing literature, we compared our cases to those previously reported. The rating severity system proposed by Van den Berg and Francke (30) was applied to correlate the phenotypic and cytogenetics changes. We observed more severe reduction defects in the upper limbs than in the lower limbs. While the main reduction defects in the upper limbs involved the thumb and radius ranging to phocomelia, absent or severely hypoplastic fibula was the main lower limb involvement. We emphasize this finding in the present investigation. Heterochromatin repulsion of chromosomes derived from Roberts syndrome patients is a characteristic cytogenetic abnormality. It was a constant finding in our studied patients demonstrated by DABI stain which supports the possibility that mutations in Roberts syndrome lie in centromere related proteins which may also play a role in body patterning. This was proved recently by Vega et al. (31). Application of the clinical rating score and its correlation with cytogenetic changes showed negative results. Cytogenetic studies in normal obligatory heterozygotes parents showed no changes. Phenotypic variability within the same family as well as between different families was observed. The ascertainment of 4 cases with Roberts syndrome from 3 Egyptian consanguineous families during one year in our department may indicate a high frequency of the Roberts syndrome allele among Egyptians. This confirms the need for molecular studies for early and accurate prenatal diagnosis to prevent such dramatic malformation syndrome.

Abnormalities, Multiple↗

PubMed2005

Unusual pattern of inheritance and orodental changes in the Ellis-van Creveld syndrome.

Ellis-van Creveld (EVC) syndrome (chondroectodermal dysplasia, mesoectodermal dysplasia, OMIM 225500) is an autosomal recessive skeletal dysplasia characterized by short limbs, short ribs, postaxial polydactyly and dysplastic nails and teeth. Oral manifestations tend to be pathognomonic such as multiple broad labial frenula and congenital missing teeth. In this study we report three Egyptian families with six cases of EVC syndrome. An unusual pattern of inheritance with father to son or to daughter transmission was observed in 2 consanguineous families thus demonstrating pseudo-dominant inheritance, probably for the first time in the literature. A new consistent orodental anomaly found in all our cases was bifid tip of the tongue. We emphasize study of orodental anomalies in future cases for accurate diagnosis of Ellis-van Creveld syndrome and its probable differential diagnosis from Weyers acrodental dysostosis.

Adolescent↗

PubMed2003

A novel point mutation of the androgen receptor (F804L) in an Egyptian newborn with complete androgen insensitivity associated with congenital glaucoma and hypertrophic pyloric stenosis.

Androgen-insensitivity syndrome (AIS) is a major cause of male pseudohermaphroditism (MPH). Although AIS is usually reported as a monogenic disease resulting from androgen receptor (AR) mutations, on rare occasions it has been observed as part of a multiple congenital anomaly syndrome. We report here a patient who was the first newborn girl of an unrelated couple. Shortly after birth, the diagnoses of congenital glaucoma and pyloric stenosis were made. A detailed history of the father's family revealed that nine members presented glaucoma before 40 years of age. Clinical and ultrasound evaluation showed two inguinal testes, with female external genitalia and no Mullerian derivatives. The patient had a 46,XY karyotype, good testicular response to gonadotrophin stimulation and a remarkably high T : dihydrotestosterone ratio. Sequencing of the five exons of the 5alpha-reductase type 2 gene (SRD5A2) was normal. Conversely, a de novo point mutation was found in exon 6 of the AR gene, resulting in an F804L substitution, which has never been described previously. To our knowledge, the association of complete AIS, congenital glaucoma and pyloric stenosis has also never been reported previously.

Androgen-Insensitivity Syndrome↗

PubMed2003

Expanding the phenotypic spectrum of the Baller-Gerold syndrome.

We report on two sisters off-spring of healthy consanguineous parents, where their major clinical features absent thumb, radial aplasia and craniosynostosis led to a diagnosis of Baller-Gerold syndrome BGS (OMIM:218600). Syndromes with associated preaxial reduction defects mainly Fanconi pancytopenia, VATER association, Rothmund-Thompson and Roberts phocomelia syndrome were excluded by proper clinical and cytogenetic studies. In addition to craniosynostosis and radial deficiency, our studied cases had absent or hypoplastic thumbs, postaxial polydactyly in the left foot, genital anomalies and orodental manifestations. Review of the literature depicted phenotypic variability of BGS. The presence of affected sibs the offspring of consanguineous parents confirms autosomal recessive inheritance. The observation of associated postaxial polydactyly, blue sclera, rotatory nystagmus, other skeletal and orodental anomalies broadened the spectrum of phenotypic variability. Awareness of the expanded phenotypic spectrum will improve the diagnosis and genetic counseling of BGS.

Abnormalities, Multiple↗

PubMed2000

Lenz microphthalmia syndrome: three additional cases with rare associated anomalies.

Lenz microphthalmia syndrome is an extremely rare inherited disorder, characterized by unilateral or bilateral microphthalmia. In rare cases affected patients exhibit complete absence of eye or blepharoptosis resulting in visual impairment. Additional physical abnormalities are often associated with this disorder, orofacial, digital, skeletal and urogenital abnormalities. Here we present three cases of Lenz microphthalmia with additional manifestations: two brothers of first cousin mating, the elder one has bilateral congenital cataract which is a rare ophthalmological finding in this syndrome and a third case who presented to us because of ambiguous genitalia. She was 12 years old, and reared as a female. Chromosomal analysis showed 46,XY karyotype, and hormonal studies indicated 5-alpha reductase deficiency. This is the first report of the association of 5-alpha reductase deficiency with Lenz microphthalmia syndrome.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed1999

Loss-of-function mutations in the cathepsin C gene result in periodontal disease and palmoplantar keratosis.

Papillon-Lefèvre syndrome, or keratosis palmoplantaris with periodontopathia (PLS, MIM 245000), is an autosomal recessive disorder that is mainly ascertained by dentists because of the severe periodontitis that afflicts patients. Both the deciduous and permanent dentitions are affected, resulting in premature tooth loss. Palmoplantar keratosis, varying from mild psoriasiform scaly skin to overt hyperkeratosis, typically develops within the first three years of life. Keratosis also affects other sites such as elbows and knees. Most PLS patients display both periodontitis and hyperkeratosis. Some patients have only palmoplantar keratosis or periodontitis, and in rare individuals the periodontitis is mild and of late onset. The PLS locus has been mapped to chromosome 11q14-q21 (refs 7, 8, 9). Using homozygosity mapping in eight small consanguineous families, we have narrowed the candidate region to a 1.2-cM interval between D11S4082 and D11S931. The gene (CTSC) encoding the lysosomal protease cathepsin C (or dipeptidyl aminopeptidase I) lies within this interval. We defined the genomic structure of CTSC and found mutations in all eight families. In two of these families we used a functional assay to demonstrate an almost total loss of cathepsin C activity in PLS patients and reduced activity in obligate carriers.

Aggressive Periodontitis↗

PubMed1998

A new multiple congenital anomaly, mental retardation syndrome with preaxial brachydactyly, hyperphalangism, deafness and orodental anomalies.

We report on a child with a 'new' syndrome characterized by multiple congenital anomalies, mental retardation, sensorineural deafness, talon cusps of upper central incisors, growth retardation, bilateral symmetrical digital anomalies mainly in the form of preaxial brachydactyly and hyperphalangism of digits I-III. Because he had a similarly affected brother and his parents were cousins we suggest autosomal recessive inheritance, X-linked recessive inheritance cannot be excluded. Differential diagnosis from other syndromes with preaxial brachydactyly and hyperphalangism is presented.

Abnormalities, Multiple↗

PubMed1997

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.

Abnormalities, Multiple↗

PubMed1997

Identification of Mediterranean beta-thalassemia mutations by reverse dot-blot in Italians and Egyptians.

beta-Thalassemia is a significant public health problem in Egypt where over 1000 of the annual 1.5 million newborns are expected to be affected with this disorder. A preventive program of the disease should be multifaceted with its technical component based on carrier screening and prenatal diagnosis through mutation detection. In addition, it should have an information and educational component with the aim of increasing public awareness of the disease. Proper selection of the technique(s) to be utilized in such a program is highly important. The appropriate technique to be used in screening should be reliable, simple and cost effective. It should also circumvent the problem of marked heterogeneity of the disease in Egypt. The reverse dot-blot technique has been used in the present study for the characterization of mutations in 138 Italian and 108 Egyptian thalassemia chromosomes, confirming its reliability as a screening method. The technique is now in routine use for thalassemia diagnosis in the Microcitemia Center of the Galliera Hospital in Genoa, Italy. Based on these results, we recommend the reverse dot-blot method as the technique of choice in the preventive program of this disease in Egypt.

Alleles↗

PubMed1997

Molecular analysis of androgen resistance syndromes in Egyptian patients.

Androgen resistance syndromes [i.e. 5 alpha-reductase deficiency (5 alpha RD) and androgen receptor (AR) defects] are frequently reported among Egyptian intersex patients. This study examined AR and 5 alpha-reductase 2 (5 alpha R2) gene mutations among a sample of such cases as a first step towards instituting a screening program. Five families with a typical hormonal profile of 5 alpha RD were screened for major deletions of exons 3-5 of the 5 alpha R2 gene, using polymerase chain reaction (PCR) and electrophoresis. Thereafter, screening for point mutations was carried out by single strand conformational polymorphism (SSCP) analysis, followed by nucleotide sequencing. Seven patients with androgen insensitivity syndrome (AIS) were subjected to molecular analysis of AR exons B-H by a similar protocol, except for the use of denaturing gradient gel electrophoresis (DGGE) for screening point mutations. No major deletions were found in either gene. One family had abnormal electrophoretic mobility on SSCP of exon 5 of the 5 alpha R2 gene, resulting from a point mutation (C to T substitution) at codon 246. Another family, showing retarded mobility on DGGE, had a point mutation (G to A substitution) at codon 889 of the AR gene. In conclusion, the study revealed two mutations previously reported in other geographically distinct populations, inferring the possibility of mutational hot spots in the genes.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed1996

Greig cephalopolysyndactyly syndrome with dysgenesis of the corpus callosum in a Bedouin family.

We report on the first known Bedouin family with Greig cephalopolysyndactyly syndrome (MIM 175700). The index patient and his father shared pre- and postaxial polysyndactyly, mild mental retardation, and corpus callosum dysgenesis. Their phenotypic findings were compared with reported cases of both Greig cephalopolysyndactyly (GCPS) and acrocallosal syndromes. This family represents the second report of the rare occurrence of dysgenesis of the corpus callosum in GCPS.

Abnormalities, Multiple↗

PubMed1996

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.

Bone and Bones↗

PubMed1996

New autosomal recessive multiple congenital abnormalities/mental retardation syndrome with craniofacial dysmorphism absent corpus callosum, iris colobomas and connective tissue dysplasia.

We report three sibs, one boy and two girls, with a similar MCA/MR syndrome, where parents were first cousins. They had macrodolichocephaly, an elongated face, apparently low-set simple ears, hypertelorism, bilateral "key-hole' colobomata of the iris, retina and choroid, a beaked nose, micrognathia and dental anomalies. Brain CT scan showed dilated ventricles and an absent corpus callosum. Skeletal anomalies included brachydactyly of the hands and feet, genua vara and flat feet. Two sibs had left ventricular enlargement, and aortic dilatation and regurgitation. Review of the literature from the London Dysmorphology Data Base (LDDB) and OMIM suggests that this family represents a new syndrome.

Abnormalities, Multiple↗

PubMed1994

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.

Adolescent↗

PubMed1993

Molecular characterization of beta-thalassemia in Egyptians.

We sought to determine the spectrum of mutations producing beta-thalassemia in Egypt using genomic PCR and a variety of mutation-screening procedures. Thirty-four beta-thalassemia and three Hb S/beta-thalassemia patients originating from different regions of Egypt were studied, and the causative mutation was found in 69 of 71 (97%) beta-thalassemia genes. Four mutations accounted for 78% of beta-thalassemia genes in this population; IVS-1, nt 110 (41%), IVS-1 nt 6 (13%), IVS-1, nt 1 (13%), and IVS-2, nt 848 (11%). The latter allele, a C-A mutation at the third nucleotide of an acceptor site consensus sequence, has been described previously only in one Egyptian, one Iranian, one Tunisian, and one Black American patient. Nine other alleles each accounted for 1-3% of beta-thalassemia genes. Among these was one codon 27 allele (Hb Knossos), two frameshift 106/107 alleles previously seen only in a Black American, and a rarely observed mutation in the distal promoter region of the beta-globin gene, -87 (C-A). Our results suggest that from a molecular genetic standpoint a beta-thalassemia prevention program based on carrier screening and prenatal diagnosis can be implemented in Egypt. In couples at risk for beta-thalassemia, the causative mutation should be identifiable in both members in 92% and in one member in the remaining 8%.

Base Sequence↗

PubMed1992

Karyotype/phenotype correlation in females with short stature.

We studied 60 females who presented with short stature. The main aim was to determine the effect of karyotype variation on phenotype. A somatic feature score was calculated for each case depending on the presence of 17 clinical somatic changes known to occur in Turner syndrome. Karyotype studies showed the following results: 45,X (n = 22): 46,XX (n = 11); 45,X/46,XX (n = 10); 46,XX/46,Xi(Xq) (n = 4); 46,XX/46,XXq- (n = 3); 46,XX/46,XXp- (n = 2); 46,Xi(Xq) (n = 2); 45,X/46,Xi(Xq) (n = 2); 46,XXp- (n = 1); 46,XX/47,XXX (n = 1); 46,XXq- (n = 1); 45,X/46,X(ry) (n = 1). Karyotype/phenotype correlation showed the gradation of severity of clinical phenotype to be related to the number of X chromosomes. The highest somatic scores and the most severe clinical manifestations were noted in cases of pure 45,X Turner and the mildest in 46,XX/46,XX(str) mosaics or pure 46,XX, including hypergonadotrophic hypogonadism. Our findings revealed a dosage effect of the X chromosome on phenotype, thus confirming that partial X chromosome inactivation modifies somatic and pubertal development. Our results also support both the additive and interactive hypotheses of karyotype/phenotype correlation.

Adolescent↗

PubMed1991

Cataract, hypertrichosis, and mental retardation (CAHMR): a new autosomal recessive syndrome.

We have studied 2 Egyptian sibs (the offspring of normal first cousins) with congenital cataract, hypertrichosis, mental retardation, and normal chromosomes. Review showed that the condition of our patients was not similar to any previously reported entity. POSSUM lists 84 syndromes with any of the above 3 main traits. Two disorders with cataract and mental retardation, Martsolf syndrome and Mollica-Pavone-Anterer syndrome, have overlapping manifestations and therefore are particularly differentiated from our cases. We suggest that the association of congenital cataract, hypertrichosis, and mental retardation observed in this report represents a new autosomal recessive syndrome.

Cataract↗

PubMed1991

Neu Laxova syndrome in two Egyptian families.

We report on 2 Egyptian girls from 2 families with 8 affected relatives, 4 in each family. The 2 propositae had unusual facial appearance, severe microcephaly, generalized edema, contractures of limbs, and generalized ichthyotic skin lesions. Findings in the present 2 patients were compared with those in previously reported cases of Neu Laxova syndrome. In our cases, consanguinity, affected sibs, and affected cousins were noted. Autosomal recessive inheritance and lethality are emphasized. A high frequency of the Neu Laxova syndrome in Egyptians is suspected as a result of the increased consanguinity rate.

Abnormalities, Multiple↗