Developmental abnormalities of mid and hindbrain: a study of 23 Egyptian patients

With the advent of neuroimaging modalities specifically, magnetic resonance imaging [MRI], recognition of developmental defects of posterior fossa has greatly improved. Is to delineate the clinical, cytogenetics and radiological features of patients with midhindbrain anomalies. Twenty-three patients with mid-hind brain malformations were included in this study. Complete clinical evaluation, cytogenetic analysis and neuroradiological study were done for each patient. Patients' sex ratio was [M: F/ 0.9:1] and the mean age was 2.17 years. Parental consanguinity was 86.9% and positive family history was recorded in 7 families. Based on clinico-radiological findings, patients were categorized as Joubert syndrome and related cerebellar disorders [34.8%], pontocerebellar hypoplasia [26.1%], lissencephaly cerebellar hypoplasia [13%], isolated cobblestone lissencephaly with normal muscle and eye [8.7%], isolated vermian hypoplasia [13%] and retrocerebellar cyst [4.4%]. Cytogenetic analysis revealed abnormalities in 3 patients [13%]; pericentric inversion of chromosome 8 in a patient with lissencephaly cerebellar hypoplasia, del 5p14.3-pter delineating Cri du chat syndrome and associated with vermian hypoplasia and del 18q21.1-qter in a patient with retrocerebellar cyst due to paternal balanced translocation t [4;18]. FISH for specific locus and whole chromosomal painting were used to document the assigned aberrations. Although most of the cerebellar malformations are of Mendelian inheritance, this study emphasizes the importance of chromosomal analysis for patients with posterior fossa anomalies. With more researches describing clinico-radiological characterization of hind brain dysgenesis will allow better understanding of these disorders, further delineation of relevant syndromes and new genes identification

Detection of steroid sulfatase gene deletion [STS] in Egyptian males with X-linked ichthyosis

Ichthyosis is a disorder of keratinization characterized by diffuse uniform and persistent scales resulting from abnormal epidermal differentiation or metabolism. Ichthyosiform dermatoses are classified into four major types, ichthyosis vulgaris, X-Linked ichthyosis, congenital recessive ichthyosis and lastly epidermolytic hypekeratosis which was previously called bullous ichthyosiform erythroderma. The identification of steroid sulfatase as the cause of X-Linked ichthyosis points to the importance of this enzyme in skin desquamation. Fluorescent in situ hybridization [FISH] analysis is a good diagnostic technique to detect a common deletion of the STS gene. Most patients with X-Linked ichthyosis have large deletions of the STS locus in this study, we aimed to detect the X-Linked type of ichthyosis, diagnosed by detection of STS gene deletions among Egyptian males. We performed this study on Egyptian males complaining of X-linked ichthyosis who were subjected to clinical examination, pedigree analysis of the family, cytogenetic studies using G-banding technique and fluorescent in situ hybridization [FISH] using locus specific probe for stereoid sulfatase [STS] gene which is located at chromosome Xp22.3. Our results showed that 11.11% of patients had nocturnal enuresis and 33.33% showed STS gene deletion by FISH study. The current study underlines the difficulty of diagnosis of X-Linked ichthyosis on the clinical features or pedigree analysis of the family in Egypt and the importance of cytogenetic and molecular cytogenetic studies for diagnosis. Fluorescent in situ hybridization [FISH] technique is a good, reliable, and rapid diagnostic tool to detect STS gene deletion. Since FISH will not detect partial deletion or point mutations, we recommended further molecular studies to reach the proper diagnosis of X-linked ichthyosis

Genetic studies of congenital contractures of limbs

Congenital contractures of limbs comprise a category of limb malformations that poses a difficult diagnostic and therapeutic problem. They can occur as an isolated defect or as part of syndromes. This study included 46 patients with congenital contractures of limbs. Cases were referred to the Limb and Skeletal Anomaly Clinic at the National Research Centre. Detailed family history, pedigree construction, physical and orodental examination, anthropometric measurements and radiological studies were carried out for all cases. Cytogenetic analysis using G-banding and high resolution techniques were carried out for 36 cases. Biochemical and neurophysiologic studies were conducted for selected cases. According to clinical phenol-type, cases were classified into 4 main categories, which were further subdivided into 16 entities. Category [I]: included congenital contractures that affected primarily the musculoskeletal system, 18 cases were in this category comprising 8 entities. Category [II]: Twenty cases had musculoskeletal involvement in addition to other system malformations or anomalies comprising 5 entities, of which 11 cases had multiple pterygium syndrome. Category [III]: Six patients in this study had musculoskeletal involvement plus lethality, CNS anomalies or mental retardation. Four were diagnosed as Pena-Shokeir syndrome, one with Aase-Smith syndrome and another case showed dup [1] [p36.1-36.2]. Category [IV]: Contracture deformities of limbs due to environmental factors, which were present in 2 cases only. Detailed genetic and clinical analysis of different cases with congenital contractures of limbs are presented in this study. Our work proved that contracture deformities of limbs due to genetic causes were the most common [44 cases], while those related to environmental causes were only present in 2 cases. This emphasizes the importance of careful clinical examination and categorization o patients with congenital contracture! of limbs and the necessity of proper genetic counseling of affected families. The study of the molecular causes of these disorders is important for the understanding of the pathogenesis hoping for their prevention, early intervention and gene therapy

Structural abnormalities of the Y chromosome: Genotype-phenotype correlation

The aim of this study was to correlate the structural abnormalities of the Y chromosome to its presenting clinical features to evaluate the phenotype-genotype correlation. The study was performed on 30 patients who had structural Y chromosome abnormalities. The cytogenetic methods included conventional G-banding, diamidino-2-phenylindole [DAPI] and fluorescent in situ hybridization [FISH] techniques. The structural abnormalities of the Y chromosome were a deletion of the long arm [Yq-] in 13 cases, a partial deletion of the short arm [Yp-] in 6 cases, large heterochromatin of Y [Yq+] in 6 cases, pericentric inversion in 4 cases and one case with ring Y. Their phenotypic presentations varied from complete normal male, ambiguous genitalia to complete female phenotype. The clinical presentations and cause of referral of the patients were variable including male infertility and azoospermia, primary amenorrhea, mental retardation, multiple congenital anomalies and/or dysmorphism, short stature, ambiguous genitalia, routine premarital counseling and repeated abortions