Role of family history and clinical screening in the identification of families with idiopathic dilated cardiomyopathy in Johannesburg, South Africa

Background. Familial disease is implicated in 20 - 50% of cases of idiopathic dilated cardiomyopathy (IDCM) worldwide. The contribution of familial factors to IDCM in the Johannesburg area, South Africa, is unknown.Objectives. To describe the demographic details of patients with IDCM who presented at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH), and to determine if there is evidence of familial disease through family history assessment and clinical screening of relatives.Methods. This was a single-centre, cohort study performed at a quaternary care centre at CMJAH. Fifty unrelated probands diagnosed with IDCM and available first- and second-degree relatives were included in the study. A three-generation family pedigree was drawn up for all 50 probands. The pedigrees were analysed to identify the presence or absence of familial disease and categorised as positive, intermediate, negative or unreliable according to the family history obtained. From the 50 proband cases, there were 21 family members available for screening for features of IDCM. Eighty-two family members (55 first-degree and 27 second-degree relatives) were screened clinically. Screening included a personal history, full physical examination, electrocardiogram (ECG) and echocardiogram.Results. The mean age at diagnosis of IDCM in the probands was 41.7 (standard deviation (SD) 12.4) years. The majority of probands were males (n=38; 76%). Of 50 pedigrees analysed, 14 (28%) were positive and likely to be indicative of familial dilated cardiomyopathy (DCM), and 9 (18%) patients were at intermediate risk of familial disease. Eighty-two asymptomatic family members were screened, with a median age of 33 (range 11 - 76) years. No asymptomatic family members were identified with features of DCM or presymptomatic DCM. Eleven of the 21 families screened had relatives with possible presymptomatic DCM identified by abnormalities on the echocardiogram in 3 families (14.3%) (4 individuals; all first-degree relatives of the index case) or identified on the basis of a conduction defect (an arrhythmia or first-/ second-/third-degree heart block) in 8 families (72.7%) (11 individuals; 9 first-degree and 2 second-degree relatives).Conclusions. Screening for IDCM should include a three-generation family history and clinical screening of all first-degree family members. As IDCM has an age-related penetrance, at-risk family members should receive follow-up for screening to assess symptoms and signs of IDCM. Genetic testing would potentially identify family members at high risk, who would benefit from screening; this might be a less expensive option

Fanconi Anaemia in South African Patients with Afrikaner Ancestry

Background. Fanconi anaemia (FA) is a rare genetic disorder of impaired DNA repair that results in physical and haematological consequences in affected individuals. In South Africa (SA), individuals with Afrikaner ancestry are at an increased risk of inheriting disease-causing FA mutations, owing to the three common FANCA (FA, complementation group A) founder mutations present in this population subgroup.Objectives. To describe the physical phenotype of SA patients with FANCA mutations for the purpose of recommending appropriate care for affected individuals.Methods. A structured clinical examination and file-based review were used to evaluate the physical phenotype of 7 patients with compound heterozygous and homozygous FANCA founder mutations, and 1 patient with confirmed FANCA complementation analysis. Descriptive statistical analysis was used to determine the frequency of physical anomalies in Afrikaner patients and to compare the described phenotype to other FA cohorts, including a previously clinically characterised black SA FA cohort.Results. An earlier age of diagnosis of FA in Afrikaner patients, a high frequency of somatic anomalies and a higher-than-expected incidence of the VACTERL/H phenotype were noted.Conclusions. Based on our findings, recommendations for the care of FA patients with Afrikaner ancestry are made, including renal ultrasound evaluation at diagnosis and hearing screening

Huntington's Disease Genetic Heterogeneity in African Patients

"Huntington's disease has been reported to occur rarely in black patients. A new genetic variant ""Huntington's disease like 2"" (HDL2); occurring more frequently in Blacks; has recently been described. The absence of an expanded tri-nucleotide repeat at the chromosome 4 HD locus was previously regarded as a way of excluding classical Huntington's disease (HD). The objective of this paper is to describe a number of black patients with genetically proven Huntington's disease and review its occurrence in Africa. Methods: Eleven black families (twelve subjects); with genetically proven Huntington's disease are described; nine from the Dr George Mukhari Hospital and two from private practice in Tshwane. Results : Chorea was present in all 12 patients and cognitive decline in nine. Nine had an age of onset between 30-50 years. Six families exhibited expansion of the trinucleotide repeat at the chromosome 4; IT 15 gene (HD) and five a Junctophilin (JPH3) trinucleotide expansion at chromosome 16 (HDL2). The HDL2 subtype showed a tendency towards a later age of onset. Conclusions: The clinical presentation of the two genotypes (i.e.; HD or HDL2) appears to be similar. The actual rate of occurrence of Huntington's disease in Blacks may require reassessment. With the number of Huntington's chorea patients occurring in our area (Garankuwa); the possibility of clustering of the condition arises."