Genetic study of patients with proportionate growth deficiency referred to human genetics clinic, in Alexandria

Growth deficiency is the term that describes a growth rate below the appropriate growth velocity for age. Normal stature varies widely among ethnic groups and within each ethnic group approximating a normal distribution. Short stature may be proportionate or disproportionate. Children with proportionate short stature may have more generalized disorders. The aim of the present work was to study the phenotypic variations in patients with proportionate growth deficiency, and to evaluate the diagnosis to provide accurate genetic counseling. The study included 53 patients with proportionate growth deficiency from those attending the Human Genetics Clinic, Medical Research Institute, Alexandria University, during a four years period. They were subjected to a complete genetic and family history, pedigree analysis, complete genetic examination, ant hropometric measurements, cytogentic analysis and others investigations when needed. The results showed that group I consisted of 17 cases [32.07%] with chromosomal anomalies [7 cases with numerical aberrations and 10 cases had structural anomalies], group II included 21 patients [39.62%] with single gene disorders [11 patient had autosomal dominant disorders. 9 cases with autosomal recessive diseases and only I case with X-linked recessive disorder]. Group Ill consisted of the sporadic syndromes [11 cases; 20.75%] and the last group had disorders due to teratogens [4 cases; 7.56%]. It is essential that a specific diagnosis should be made because there are hundreds of causes for growth deficiency that have differing prognoses, complications and responses to treatments

X-linked disorders among patients with suspected genetic disorders attending the genetic clinic in Alexandria

A total of 1825 patients referred to the Genetics Clinic, Medical Research Institute, Alexandria University were assessed to determine the frequency of X-linked disorders. It was found that 3.0% [55/1825 cases; 52 males and 3 females] had X-linked disorders; 31.0% [17/55] had fragile X-syndrome 21.8% [12/55] had androgen insensitivity syndrome, 14.5% [8/55] had muscular dystrophy, 14.5% [8/55] had biochemical disorders and 18.2% [10/55] had X-linked syndromes. The frequency of consanguinity among parents of cases with X-linked disorders was 29.1%. Positive family history was detected in 29.1% of cases. These findings are crucial for geneticists and genetic counsellers in their evaluation, diagnosis, counseling and management of patients

molecular study of methylenetetrahyrofolate reductase gene in mothers of standard down syndrome patients

The observation that a lot of children with Down syndrome are born to mothers with young age made it important to identify the mechanisms involved in this young age group. It was found that DNA hypomethylation is associated with chromosomal instability and abnormal chromosome segregation. This knowledge led to the clarification of the role of enzymes involving in the methylation reaction like Methylene Tetrahydrofolate Reductase enzyme [MTHFR]. The C-T common polymorphism at nucleotide 677 [C677T], which results into an alanine to valine substitution in the MTHFR protein, caused higher thermolability and reduced enzyme activity in lymphocyte extracts. In order to verify this association, we studied the presence of the C677T polymorphism of the MTHFR gene in 50 mothers of Down syndrome children and 50 control mothers. A non-significant higher incidence of the mutant T allele in Down syndrome children mothers [6%] than in control [2%] was detected. These results do not support the presence of an increased risk of Down syndrome mothers carriers of the T allele in Egyptian population

Genetic study of multiple congenital contractures [Arthrogryposis Multiplex Congenita]

This work was carried out to study different conditions with arthrogryposis and their mode of inheritance that would allow proper diagnosis, management and appropriate genetic counseling. The study included 30 patients with arthrogryposis attending the Genetic Clinic, Medical Research Institute, Alexandria University. The frequency of parental consanguinity was 50%. An abnormal pregnancy history was found in 22 cases. Both upper and lower limb affections were noticed in twenty-eight patients, while isolated upper limb affection occurred in one case and isolated lower limb affection in one case. Finger joints were the most commonly affected. It was concluded that the examination of all joints in the upper and lower limbs is the key of diagnosis in the majority of cases of arthrogryposis. There is a marked inter- and intra-familial variability in many conditions with arthrogryposis. An accurate diagnosis is important in genetic counseling, prevention, management and prognosis

Chromosome anomalies in normal androgenized infertile males

Chromosome anomalies are known to play a role in human infertility. Chromosome analysis of 103 normal androgenized infertile azoospermic [97.1%] or oligospermic [2.9%] males revealed that the frequency of chromosomal abnormalities was 8.7%. Two patients [1.94%] had a 46,XX chromosome complement, one patient [0.97%] had a 45,X karyotype, two patients [1.94%] had a 45,XY,t[13;14][p11;q11] karyotype, one patient [0.97%] had a 46,XY,inv[9][p12;q13] chromosome constitution, two patients [1.94%] had a 46,XY,del[Y][q12] karyotype, and one patient [0.97%] had a 45X/46,X+marker the nature of which was not clarified

Phenotypic implications of cytogenetic findings in female patients with short ststure turner and noonan syndromes

This study included 37 females with short stature and/or delayed puberty. They were subjected to complete clinical genetic examination, X-rays, cytogenetic analysis and anthropometric measurements, which included 14 measurements and 8 derived indices. Patients with structural abnormality of X chromosome [22.6%] showed mild phenotypic manifestations, while the mosaic group [32.3%] exhibited a phenotype moderate in severity. Analysis of the anthropometric measurements and indices showed that TS had an abnormal growth pattern more evident in pure TS and mosaic groups. Comparison between patients with TS [83.8%] and Noonan syndrome [16.2%] showed that both had tendency to growth retardation with similar growth pattern in the 2 conditions. Early diagnosis, assessment of growth with follow up will aid in both management and genetic counseling in Turner and Noonan syndromes

Genetic, clinical, radiological study of monogenic phakomatoses

The study comprised 29 patients with features suggestive of phakomatoses refered to the Human Genetic Clinic, Medical Research Institute, and Dermatology Department, Faculty of Medicine, Alexandria University. All the patients were subjected to complete genetic history, pedigree analysis, clinical genetic, dermatological examinations, radiological investigations [X-ray, Ultrasonography and CT] and cytogenetic study in some patients. The result revealed that: 19 patients had neurofibromatosis [NF], 17 had NF I, one patient had Cafe au-lait type and the last one had segmental type. NF is the most common type of phakomatoses and is inherited as autosomal dominant. Eight patients had chromosomal instability syndromes [4 had xeroderma pigmentoza, 2 had De Sanctis Cacchione syndrome and 2 had ataxia telangiectasia]. Increased chromosomal breaks among these patients were detected by special technique. Chromosomal instability syndromes are inherited as autosomal recessive. The last 2 female patients were diagnosed as focal dermal hypoplasia syndrome [FDH] which is an X-linked dominant phakomatoses. In phakomatoses regular follow up examination and genetic counseling with emphasis on new symptoms are necessary to allow early intervention, detection of

Cytogenetic findings in moderate and severe mental handicapped males

The aim of the present study was to estimate the frequency of various chromosomal abnormalities among the mentally handicapped males. A cytogenetic study done for 300 males with mental handicap, attending the Genetic Clinic, Medical Research Institute, Alexandria University, from institutions of the mentally retarded in Alexandria. 71 males [23.7%] has an abnormal karyotypes, 48 [16.0%] had Down syndrome, one [0.3%] had autosomal non-Down syndrome, 7 [2.3%] had structural autosomal aberrations other than Down syndrome [5 unbalanced, 2 balanced], 13 [4.3%] had fragile X-chromosome while, 2 [0.7%] had sex chromosome abnormalities. Chromosomal aberrations are important cause of mental handicap