One gene, many phenotypes

Phenotype descriptions are valuable information right at the interface of medicine and biology. With the rapid advancement in the fi eld of genetics, thousands of genes involved in human diseases have been cloned. It was expected that knowledge of mutations would lead to consistent genotype-phenotype correlations. The understanding of mechanisms underlying genotype-phenotype discrepancies is important, as it will move clinical genetics towards predictive medicine, allowing better selection of therapeutic strategies and individualized counseling of persons affected with genetic disorders.Keywords: Gene, phenotype, mosaicism, epigenetics, pleiotropy

Congenital malformations prevalent among Egyptian children and associated risk factors

According to the World Health Organization the term congenital anomaly includes any morphological, functional, biochemical or molecular defects that may develop in the embryo and fetus from conception until birth, present at birth, whether detected at that time or not. Based on World Health Organization report, about 3 million fetuses and infants are born each year with major malformations. Several large population based studies place the incidence of major malformations at about 2–3% of all live births. In this study we tried to assess the frequency and nature ofcongenital malformations (CMs) among Egyptian infants and children as well as the associated maternal, paternal and neonatal risk factors. Patients (13,543) having CMs were detected among 660,280 child aged 0–18 years attending the Pediatric Hospital Ain Shams University during the period of the study (1995–2009), constituting 20/1000. Males were more affected than females (1.8:1). According to ICD-10 classification of congenital malformations the commonest system involved were, nervous system, followed by chromosomal abnormalities, genital organs, urinarysystem, musculoskeletal, circulatory system, eye, ear, face, and neck, other congenital anomalies, digestive system, cleft lip and palate, and respiratory anomalies. Among the maternal risk factors detected were multiparity, age of the mother at conception, maternal illness, exposure to pollutants, and intake of the drugs in first months. Consanguineous marriage was detected in 45.8% of patients. Surveys of CMs must be done in every country to provide prevalence, pattern of occurrence, nature, identify causes, and associated risk factors to prevent or reduce the occurrence of CMs

Hereditary periodic fever syndromes

Hereditary periodic fever syndromes, comprise a group of hereditary disorders with similar clinical features of recurrent short episodes of fever associated with inflammatory manifestations. These are usually self-limited in nature and occur in the absence of infection or autoimmune reaction. Between attacks, patients feel well and regain their normal daily functions until the next episode occurs. The episodes are usually associated with elevated serum levels of acute-phase reactants (e.g., fibrinogen, serum amyloid A [SAA]), an elevated erythrocyte sedimentation rate (ESR), and leukocytosis. These illnesses represent inborn errors in the regulation of innate immunity thus substantiating the distinction from autoimmune disorders, which more directly affect the adaptive immune system. Each of these disorders has a distinct genetic defect. Most of these proteins are members of the Death Domain Superfamily and are involved in inflammation and apoptosis. These proteins mediate the regulation of nuclear factor-kB (NF-kB), cell apoptosis, and interleukin 1b (IL-1b) secretion through cross-regulated and common signaling pathways. Six periodic fever syndromes have been characterized. Genetic defects, pathogenesis, epidemiology and management of these fevers will be discussed.Keywords: Periodic fever syndromes; Pyrin; Cryopyrin; Autoinflamatory; diseases; Mevalonic kinas

C syndrome in an Egyptian infant with dilated brain ventricles and heteroto pia

C syndrome is an autosomal recessive disorder characterized by trigonocephaly, partial or complete obliteration of the metopic suture which is characteristic, and short limbs. In this paper we describe an Egyptian boy affected with this syndrome, with no exophthalmos and with dilated brain ventricles and heterotopia. Keywords: C syndrome, trigonocephaly, cutaneous syndactyly, metopic sutureEgyptian Journal of Medical Human Genetics Vol. 9 (2) 2008: pp. 257-26

Abnormal presentation of Peters’ anomaly in a family with microcornea cataract syndrome

A case of Peters’ anomaly with bilateral crease on ear lobule and hypospadiuswas reported in a family with microcornea, cataract syndrome. The eyes hadall the features of Perters’ Anomaly. The combination of these fi ndings has not been reported in literature to our know ledge, making this case a unique one.Keywords: Peters’ anomaly, persistent papillary membrane, ear lobule crease, hypospadius, microcornea, cataract syndrome

Genetics of obesity

There is now widespread recognition that the continuing increase in the prevalence of obesity seen in many countries is likely to have major adverse effects on public health. The National Center for Health Statistics reports that 61% of adults in the United States are overweight and 26% are obese. Also The National Health and Nutrition Examination Survey IV, 1999–2002, documents that 16% of children are overweight and 31% are at risk of becoming overweight or are already overweight, representing nearly a 300% increase since the 1960s. The genetic influences are likely to be particularly powerful in people with severe and early-onset obesity, the group is most likely to suffer adverse clinical consequences. In this review we will discuss the Genetics of body weight regulation including genes encoding factors regulating food/energy intake, genes encoding factors implicated in energy expenditure, and genes encoding factors implicated in adipogenesis as well as syndromic forms of obesity.Keywords: Obesity; Body weight regulation; Obesity syndrome

Frontofacionasal dysplasia: another observation

Frontofacionasal dysplasia (FFND) is a rare group of disorders, characterized by ocular hypertelorism and frontonasal process anomalies in which clinical and etiological heterogeneity have been recognized since the first review by Gollop 1981.1 Frontofacionasal dysplasia is inherited as an autosomal recessive genetic trait. We report on a 10 month old male whose parents are non consanguineous. The patient has severe craniofacial anomalies characterized by: hypertelorism, unilateral (Right sided) malformed eye, lagophthalmos, irregular Sshaped palpebral fissures, deformed nostrils, hypoplastic nasal wing, cleft lip, cleft palate and meningeocele. This association of anomalies suggests the diagnosis of frontofacionasal dysplasia and in our case is associated with facial heamangioma. To our knowledge, facial heamangioma in association with FFND have not been described before Keywords: Hypertelorism, facial hemangioma, frontofacionasal dysplasia. Egypt. J. Hum. Genet Vol. 8 (2) 2007: pp. 225-22

Thalassemia intermedia: An overview

β-Thalassemia is considered the most common chronic hemolytic anemia in Egypt. Patients with β-thalassemia whose anemia is not so severe as to necessitate regular transfusions are said to have thalassemia intermedia. It is characterized by a significant genetic and clinical heterogeneity. The clinical phenotype ranges between the severe, transfusion-dependent thalassemia major and the asymptomatic carrier state. Thalassemia intermedia represents up to one-fourth of β-thalassemia patients. It is essential to discuss the reasons for the remarkable heterogeneity and natural history of thalassemia intermedia so that an effective method for the control and management of thalassemia intermedia can be established. This review will outline the genetics of hemoglobin biosynthesis as well as an overview on the pathogenesis, molecular basis, hematologic and clinical features of thalassemia intermedia, in addition to management of complications affecting patients with such disorder.Keywords: Globin genes; LCR; Thalassemia modifiers; Haplotypes; Managemen

Holoprosencephaly:a report of 2 cases with different presentations

Holoprosencephaly is a common developmental defect of the forebrain and midface in humans. Clinical expression is variable, extending in unbroken sequence from a small brain with a single cerebral ventricle and cyclopia to clinically unaffected carriers in familial holoprosencephaly. Here, we describe two unrelated affected cases, with alobar, and semilobar holoprosencephaly with different presentations and clarified the associated phenotypic changes in form of microcephaly, hypotelorism, flat nose, a single nostril, a midline cleft lip and palate in the first case and solitary median maxillary central incisor, associated with prominent midline palatal ridge in the second case Keywords: Holoprosencephaly, ocular hypotelorism, central incisor, microcephaly, cleft lipEgyptian Journal of Medical Human Genetics Vol. 9 (2) 2008: pp. 249-25

Goldenhar syndrome with skin tags on the chest wall

Goldenhar syndrome is a congenital condition that is associated with abnormalities of the head and the bones of the spinal column. The abnormalities of the head can include anomalies of the eyes, ears, facial bones, and mouth. These anomalies are extremely variable in severity. The exact cause of Goldenhar syndrome remains unknown. The etiology of this rare disease is not fully understood, as it has shown itself variable genetically and of unclear causes. This work reports a case of Goldenhar syndrome in a 1-year-old female, who presented some of the classical signs of this rare condition including Hemifacial Microsomia, epibulber dermoid tumor and preauricular skin tags. However, vertebral anomalies, deafness, renal and cardiac anomalies were absent. Skin tags on the anterior chest wall were reported in this patient for the first time.Keywords: Hemifacial Microsomia; Oculo–Auriculo–Vertebral Dysplasia; Epibulber dermoid tumor; Goldenhar syndrom