Jennifer Kromberg

Fetal Valproate Syndrome: Clinical and Neuro‐developmental Features in Two Sibling Pairs

The clinical and neurodevelopmental features are presented of four children–two sibling pairs–who were exposed in utero to valproic acid. One of each pair of children presented for diagnosis and assessment of developmental delay; the other sibling was examined at a later date. Three of the children were globally developmentally delayed with marked speech disability, and had dysmorphic features consistent with fetal valproate syndrome. One also had features of infantile autism. The fourth child had some of the dysmorphic features connected with fetal valproate syndrome, but had normal intellect, with his verbal ability being significantly below his non‐verbal ability. He currently attends a school for learning‐disabled children.

Albinism and skin cancer in Southern Africa

The presence of skin cancer was investigated in 111 albinos belonging to the black (Negro) population of Johannesburg, South Africa. The overall rate was 23.4%, the risk increasing with age. Identifiable risk factors included: environmental exposure to ultraviolet radiation; inability to produce ephelides (‘freckles’); and possibly ethnicity. The head was the site most commonly affected, and squamous was far more common than basal cell carcinoma. No melanomas were detected. Recommendations are made regarding prevention of skin cancer in the at‐risk group.

Red or rufous albinism in Southern Africa

Red or rufous albinism is a rare type of oculocutaneous albinism described, but not as yet fully investigated, in Africa and New Guinea. Twelve rufous albino subjects from 10 families participated in this preliminary study. The prevalence of rufous albinism was found to be approximately one in 8,580 among school children in the negroid population. The combination of the unusual red skin colour, ginger to reddish hair colour, low susceptibility to sun damage, and minimal visual problems, in affected individuals, suggested that they form a group which is distinct from the brown and other types of albinism. The mode of inheritance was found to be recessive. Tyrosinase assays showed that rufous albinos are tyrosinase positive and on electron microscopy studies normal melanosomes and melanocytes were observed in hair bulbs and skin. Visual evoked potential testing did not show the gross decussation abnormalities of the optic pathway detected in other types of albinism. Rufous albinism might be at one end of the spectrum of types of oculocutaneous albinism and, because affected people have such mild symptoms, their inclusion in this group might be debatable.

The Utilization and Outcome of Diagnostic, Predictive, and Prenatal Genetic Testing for Huntington Disease in Johannesburg, South Africa

BACKGROUND Huntington disease (HD) is an autosomal dominant neurodegenerative disorder for which genetic counseling and testing are available in South Africa. OBJECTIVE The purpose of this study was to assess the utilization of the services available in Johannesburg for diagnostic, predictive, and prenatal genetic testing and counseling for HD and the characteristics of the patients who use them. SUBJECTS AND METHODS A retrospective study was conducted using records of patients (n=287) who had genetic counseling and/or testing for HD through the Division of Human Genetics, National Health Laboratory Service and University of the Witwatersrand, Johannesburg, between January 1998 and December 2006. Age, gender, number of children, ethnicity, and test results were analyzed. RESULTS Of the 287 patients included in this study, 77% had diagnostic testing, 20% predictive, and 3% prenatal testing. In the diagnostic group, 47% of subjects tested positive for HD1 and 9% for HDL2 (all Black or of mixed ancestry). Altogether, 66.7% of subjects in the predictive group had testing and 39.5% were positive. In both groups, White subjects were overrepresented. In seven prenatal tests, three fetuses (including a set of twins) tested positive for HD and termination of pregnancy was requested. DISCUSSION AND CONCLUSION The HD services for predictive and prenatal testing appear to be underutilized, especially by Black individuals, possibly because of lack of awareness among these individuals and among healthcare providers and/or a lower HD prevalence in this group. Recognition of and testing for HDL2 is important in South Africas large Black population, and HD testing services cannot be considered complete unless testing for both HD1 and HDL2 are undertaken.

In Southern Africa, Brown Oculocutaneous Albinism (BOCA) Maps to the OCA2 Locus on Chromosome 15q: P-Gene Mutations Identified

In southern Africa, brown oculocutaneous albinism (BOCA) is a distinct pigmentation phenotype. In at least two cases, it has occurred in the same families as tyrosinase-positive oculocutaneous albinism (OCA2), suggesting that it may be allelic, despite the fact that this phenotype was attributed to mutations in the TYRP1 gene in an American individual of mixed ancestry. Linkage analysis in five families mapped the BOCA locus to the same region as the OCA2 locus (maximum LOD 3.07; theta=0 using a six-marker haplotype). Mutation analysis of the human homologue of the mouse pink-eyed dilution gene (P), in 10 unrelated individuals with BOCA revealed that 9 had one copy of the 2.7-kb deletion. No other mutations were identified. Additional haplotype studies, based on closely linked markers (telomere to centromere: D15S1048, D15S1019, D15S1533, P-gene 2.7-kb deletion, D15S219, and D15S156) revealed several BOCA-associated P haplotypes. These could be divided into two core haplotypes, suggesting that a limited number of P-gene mutations give rise to this phenotype.

Cultural Influences on the Perception of Genetic Disorders in the Black Population of Southern Africa

A multitude of rapid changes are occurring at present in South Africa but cultural transformation has been taking place for centuries, particularly since the 1400s when European explorers first set foot on the southern tip of the African continent. If culture is defined as a total way of life of a people, or the social legacy the individual acquires from the group, or that part of the environment that is the creation of man (Kluckhohn 1965), then it is obvious that the life of a group cannot remain unaltered when it comes into contact with another group, especially when the latter group has skills unknown and attractive to the former. However, when the latter group starts offering health services to the former, who, despite adopting some of the ways of the new culture, still have many of the old ways of their own culture ingrained in them, many problems may arise. It is therefore essential, if these problems are to be anticipated or forestalled, that the cultural influences on the perceptions of both genetic disorders and genetic service provision be understood.

Maternal non‐recognition of Down syndrome in black South African infants

Down syndrome (DS), one of the commonest causes of mental retardation in Caucasoids, has only rarely been described in Africa. In previous studies it was suggested that there may be clinical difficulties in making the diagnosis in African neonates. In the present study data were collected by means of a questionnaire administered partly before and partly after a genetic counselling session, to 35 mothers of African infants with DS. The results show that 83% of these mothers did not recognise any facial difference between their affected infant and other normal infants and 57% did not observe any other physical differences. After counselling, 40% of the sample still did not accept that their infant was different from other newborns. Only one mother was aware of infants with similar characteristics. These findings suggest that if mothers themselves cannot see the differences between their DS children and normal children, clinical diagnosis based on physical stigmata may be difficult. Furthermore, acceptance of the diagnosis may be retarded until delayed milestones can be observed in the affected infants.

Intellectual Disability In Rural Black Children In The Bushbuckridge District Of South Africa

Abstract The aim of this project was to investigate the prevalence and aetiology of intellectual disability in rural black children in the Bushbuckridge district. Children (aged 2–9 years) were screened by local trained field-workers who interviewed the caregivers with a simple questionnaire. Children who screened positive were examined by a paediatrician. Altogether 4581 children were screened, 541 had a paediatric assessment, and 152 (3,3%) were found to have an intellectual disability (IQ ≤ 80). The mild to severe disability ratio was 4:1, and 52% of affected children with an IQ ≤ 70 had associated disorders. The aetiology of the disability was congenital in 25% of cases, acquired in 11% and undetermined in 64%. The affected male to female ratio was 3:2. These findings have implications for the provision of appropriate special education, as well as health preventive services.

Studies on Albinism in the South African Negro I. Intellectual Maturity and Body Image Differentiation

Twenty-eight South African Negro albinos have been tested for intellectual maturity and body image boundary, characteristics and a comparison made with carefully matched normally pigmented controls. The albinos were found to be more intellectually mature than the controls but the control group showed slightly more diffuse body image boundary differentiation than the albino group.

Phenotypic consequences in black South African Fanconi anemia patients homozygous for a founder mutation

Purpose:Fanconi anemia is a genotypically and phenotypically heterogeneous condition, characterized microscopically by chromosomal instability and breakage. Affected individuals manifest growth restriction and congenital physical abnormalities; most progress to hematological disease including bone marrow aplasia. Black South African Fanconi anemia patients share a common causative founder mutation in the Fanconi G gene in 80% of cases (637_643delTACCGCC). The aim of this study was to investigate the genotype–physical phenotype correlation in a cohort of individuals homozygous for this mutation.Methods:Thirty-five black patients were recruited from tertiary level hematology/oncology clinics in South Africa. Participants were subjected to a comprehensive clinical examination, documenting growth, congenital anomalies, and phenotypic variability.Results:Descriptive statistical analysis showed significant growth abnormalities in many patients and a high frequency (97%) of skin pigmentary anomalies. Subtle anomalies of the eyes, ears, and hands occurred frequently (≥70%). Apart from malformations of the kidney (in 37%) and gastrointestinal tract (in 8.5%), congenital anomalies of other systems including the cardiovascular and central nervous systems, genitalia, and vertebrae were infrequent (<5%).Conclusion:The diagnosis of Fanconi anemia in black South African patients before the onset of hematological symptoms remains a clinical challenge, with the physical phenotype unlikely to be recognized by those without dysmorphology expertise.Genet Med 16 5, 400–406.