BACKGROUND. Neural tube defects (NTDs) are an important category of birth defect, but surveillance remains inadequate in South Africa. OBJECTIVES. To assess the identification of NTDs at a tertiary hospital using a range of prenatal, perinatal and postnatal data sources, and to estimate the impact of prenatal diagnosis and birth prevalence for the referral area. METHODS. Cases of anencephaly, encephalocele and spina bifida (SB) in a 6-year period were retrospectively identified from 5 data sources covering prenatal, perinatal and postnatal care. These were cross-correlated to avoid duplicate entries and to determine the contribution of different data sources. Details of prenatal diagnosis and termination of pregnancy (TOP) were obtained for 10 years, and birth prevalence over 2 years. RESULTS. During a 6-year period 195 NTDs were identified at a Western Cape Province tertiary hospital. These included 59 (30%) cases of anencephaly, 28 (14%) of encephalocele and 108 (55%) of SB. The majority of NTDs (71%) were detected prenatally, although SB was less commonly diagnosed prenatally than cranial defects (56% v. 88%; p<0.001). Of SB cases ascertained pre- or postnatally, 57% of patients were born alive and 50% discharged alive, but 72% of survivors had not been diagnosed prenatally. Women receiving prenatal diagnosis of any type of NTD before 24 weeks' gestation were nearly always offered TOP, and the majority accepted termination after non-directive counselling. For SB, later prenatal diagnosis was associated with much lower termination rates because the option was less often offered (51% v. 100%; p<0.001), and perhaps less often accepted (57% v. 78%; p=0.06). The estimated NTD birth prevalence for the referral area was 0.76 - 0.80 per 1 000 live births, but perhaps up to 1.18 per 1 000 when considering under-referral of lethal cranial lesions from rural areas. CONCLUSIONS. A substantial number of NTDs can be ascertained from a tertiary hospital environment if multiple data sources are used, even though adding data from the Perinatal Problem Identification Program for outlying health facilities increases detection of lethal defects. Hospital-based surveillance can be considered, especially for SB. Prenatal diagnosis was fairly common and pregnancy termination was often offered and accepted if detected before 24 weeks' gestation. A regional prenatal ultrasound programme, predominantly based in primary care but with ready access to a tertiary centre, can be quite effective, although limited or delayed access to prenatal diagnosis must be addressed.

Two of the most common cancers are breast cancer and colorectal cancer. Up to 10% of cases of each are associated with a high risk of recurrence in an affected individual, or of occurrence in biological relatives. This results from the presence of an underlying mutation (or 'pathogenic variant') in a high-penetrance gene. Such cases are typically associated with an autosomal dominant pattern of inheritance, although this may not be obvious in the family history. Genetic testing can identify many (but not all) of these cases, and should be offered to those whose family history or clinical features suggest a high risk. Although testing for certain risk genes (e.g. BRCA1 or BRCA2) has been available for years, the advent of next-generation sequencing gene panels' now allows for simultaneous testing of many more genes at lower cost. This allows for more frequent detection of pathogenic variants in underlying genes than in the past, but also makes interpretation more complex. An index of suspicion for genetic cancers and appropriate referral to a genetics health professional are increasingly important.

Rubinstein-Taybi syndrome (RSTS) is an uncommon genetic disorder characterised by a typical facies, small stature, broad angulated thumbs and intellectual impairment. Dental changes are a minor, yet significant component of the condition. Craniofacial growth retardation in RSTS is frequently complicated by unerupted teeth, while dental caries is related to the inherent intellectual deficit. Dental problems necessitate interdisciplinary management in terms of oral surgery, conservative dentistry, periodontics and orthodontics. When affected individuals are unco-operative, certain dental procedures may warrant general anaesthesia. In these instances, dental and medical staff will combine their expertise to enhance the well-being of the patient. In addition, specific dental changes may alert the medical practitioner to the possible diagnosis of RSTS. In this article we document the oro-dental manifestations and review the oro-dental approach in the management of three patients with RSTS. Our experience in South Africa may be relevant to other countries at a similar stage of development.

BACKGROUND: Fetal alcohol syndrome (FAS) is common in parts of South Africa; rural residence is a frequently cited risk factor. We conducted a FAS school prevalence survey of an isolated rural community in a West Coast village of Western Cape Province, so obtaining the first directly measured rate, focusing specifically on a South African rural area, of FAS and partial FAS (PFAS). METHODS: The study area (Aurora village), a community of about 2 500 people in a grain-producing region, has one primary school. All learners were eligible for study inclusion. Initial anthropometry screening was followed by a diagnostic stage entailing examination by a dysmorphologist for features of FAS, neurodevelopmental assessment, and an interview assessing maternal alcohol consumption. RESULTS: Of 160 learners screened, 78 (49%) were screen-positive, of whom 63 (81%) were clinically assessed for FAS. The overall FAS/PFAS rate among the screened learners was 17.5% (95% confidence interval 12.0 - 24.2%), with 16 (10.0%) children having FAS and 12 (7.5%) PFAS. High rates of stunting, underweight and microcephaly were noted in all learners, especially those with FAS or PFAS. Five (18%) mothers of affected children were deceased by the time of assessment. CONCLUSION: We describe very high rates of FAS/PFAS in an isolated rural part of the Western Cape that is not located in a viticultural region. Our study suggests that the prevalence of FAS may be very high in isolated communities, or in particular hot-spots. It adds to the growing evidence that FAS/PFAS is a significant, and underestimated, health problem in South Africa. Expanded screening and surveillance programmes, and preventive interventions, are urgently needed

BACKGROUND: Genetic testing for BRCA mutations has been available in the Western Cape of South Africa since 2005, but practical implementation of genetic counselling and testing has been challenging. OBJECTIVE: To describe an approach to breast cancer genetic counselling and testing developed in a resource-constrained environment at Tygerberg Hospital in Cape Town, Western Cape. METHODS: Genetic counselling is offered in a stepwise manner to our diverse patient population, with a focus on affected probands, and subsequent cascade testing. A record review of BRCA testing between 2005 and 2011 was performed. RESULTS: During this period 302 probands received genetic testing, with increasing numbers tested over time. Of 1 520 women treated for breast cancer since 2008, 226 (14.9%) accepted BRCA testing, and 39 tested positive (17.3% of those tested, and 2.6% of all women). Common founder mutations were detected in 11.9% of women (36/302), and comprised 73% (36/49) of mutations detected. Cascade testing increased after 2010: 16 female and 4 male family members of 19 probands accepted testing, with 6 positives being detected. CONCLUSION: A protocol-driven approach focusing on probands, with initial pre-test counselling by primary care staff has proven effective in establishing the service. Involvement of a clinical geneticist/genetic counsellor has permitted more detailed post-test counselling and increased use of cascade testing.

OBJECTIVE: The prenatal screening programme for Down syndrome (DS) in the South African public health sector remains primarily based on advanced maternal age (AMA). We assessed the changes over time and effectiveness of this screening programme within a Cape Town health district. METHODS: Retrospective analysis of the Groote Schuur Hospital Cytogenetic Laboratory and Pregnancy Counselling Clinic databases and audit of maternal delivery records at a primary health care facility. RESULTS The number of amniocenteses performed for AMA in consecutive 5-year periods reduced progressively from 786 in 1981 - 1985 to 360 in 2001 - 2005. Comparing prenatal with neonatal diagnoses of DS, the absolute number and the proportion diagnosed prenatally have remained relatively constant over time. The Pregnancy Counselling Database showed that, of 507 women receiving genetic counselling for AMA in 2008 - 2009, 158 (31.1%) accepted amniocentesis - uptake has reduced considerably since the early 1990s. The audit of women delivering at a primary care facility found that only 10 (16.4%) of 61 AMA women reached genetic counselling in tertiary care: reasons included late initiation of antenatal care and low referral rates from primary care. CONCLUSION: Prenatal screening and diagnosis for DS based on AMA is working ineffectively in the Cape Town health district assessed, and this appears to be representative of a broader trend in South Africa. Inclusion of fetal ultrasound in the process of prenatal screening for DS should be explored as a way forward.

Vertebrate gap junctions are aggregates of transmembrane channels which are composed of connexin (Cx) proteins encoded by at least fourteen distinct genes in mammals. Since the same Cx type can be expressed in different tissues and more than one Cx type can be expressed by the same cell, the thorough identification of which connexin is in which cell type and how connexin expression changes after experimental manipulation has become quite laborious. Here we describe an efficient, rapid and simple method by which connexin type(s) can be identified in mammalian tissue and cultured cells using endonuclease cleavage of RT-PCR products generated from "multi primers" (sense primer, degenerate oligonucleotide corresponding to a region of the first extracellular domain; antisense primer, degenerate oligonucleotide complementary to the second extracellular domain) that amplify the cytoplasmic loop regions of all known connexins except Cx36. In addition, we provide sequence information on RT-PCR primers used in our laboratory to screen individual connexins and predictions of extension of the "multi primer" method to several human connexins.