A clinical and molecular investigation of two South African families with Simpson-Golabi-Behmel syndrome

Background. Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked recessive overgrowth syndrome manifesting primarily in boys and characterised by macrosomia, distinctive facial features and multiple congenital abnormalities. Although this rare condition is thought to be underdiagnosed, making a diagnosis is important as affected boys have a 7.5% risk of developing visceral tumours and surveillance is warranted. Mutations in GPC3 are found in up to 70% of boys affected with SGBS.Objectives. A clinical and molecular investigation of two boys with SGBS, probands B and S, and their mothers. Documentation of the clinical phenotype could assist with diagnosis in affected boys and will lead to early initiation of tumour surveillance.Methods. Hospital folders were reviewed and clinical consultations arranged for both probands and their mothers. Molecular investigations initially searched for whole-exon deletions in GPC3 followed by gene sequencing.Results. The clinical phenotype of both probands was consistent with that previously reported in the literature. The main features pointing towards the diagnosis were macrosomia, coarse facial features and macroglossia with a midline groove in the tongue. Proband B developed a Wilms tumour. He was found to have a novel mutation causing a premature stop codon.Conclusions. This research represents the first published report of SGBS in South Africa. Early recognition and confirmation of this condition is important in order to institute tumour surveillance and assist families with accurate recurrence risks

Investigating developmental delay in South Africa: A pragmatic approach

Global developmental delay and intellectual disability are common disorders in every population, with a prevalence of 1 - 5%. Although a specific cause is not always immediately identifiable, for many affected people the aetiology is genetic or the result of secondary insult to the developing brain. Investigating children with intellectual developmental disorders (IDD) may be a significant challenge, especially in resource-limited settings. Comprehensive clinical evaluation is the first step and frequently determines the direction of further investigations. Hearing and vision screening and thyroid function tests should be performed in most patients. Children with neurological findings should undergo brain imaging, and careful consideration should be given to potential metabolic disorders in all children with IDD, a number of whom are amenable to treatment. Most children in whom a specific direction is not suggested after history-taking and examination, should be tested for chromosomal abnormalities, ideally with chromosomal microarray, which has a diagnostic detection rate of 8 - 20% in IDD. Additional tests may be indicated in particular settings, including broad-based testing for single-gene disorders, such as next-generation sequencing gene panels or exome analysis. All genetic testing has the potential of finding variants of uncertain significance, particularly when there are limited population data, such as in Africa. Making a specific diagnosis in IDD is of benefit to patients, their families and society. Therefore, a rational approach to investigating this group of patients is essential to maximise the health benefit in a cost-effective way

The burden of sickle cell disease in Cape Town

Background. South Africa has a low incidence of sickle cell disease (SCD). However, its demographics are changing because of immigration from sub-Saharan African countries where SCD is prevalent.Objectives. We aimed to determine the frequency of SCD presenting to the Haematology/Oncology Service at Red Cross War Memorial Children’s Hospital in Cape Town and to measure the associated disease burden.Methods. This was a retrospective cross-sectional study of patients first attending the Haematology Service between January 2001 and June 2010.Results. A total of 58 SCD patients were indentified, with an annual frequency that increased over the study period by 300 -400%. Up to 93.1% (n=54) were originally from other African countries, mainly the Democratic Republic of Congo (62.1%, n=36). One patient had sickle D-Punjab genotype, and all the other patients had the homozygous sickle cell anaemia genotype (Hb SS). Their haematological parameters  demonstrated a normocytic anaemia with high white cell counts. The mean number of clinic visits per patient per year was 22.2 (range 0 - 64), and the mean number of hospital admissions per patient per year was 1.2 (range 0 - 5). All the patients were on antibiotic prophylaxis. The majorityhad at least one blood transfusion (65.5%, n=38), and a significantproportion required intravenous analgesia on admission (29.3%, n=17) and hydroxyurea treatment (36.2%, n=21).Conclusions. Over the past 10 years the frequency of SCD has increased considerably, imposing a significant burden and new challenges to the health services in Cape Town

Dental needs of intellectually disabled children attending six special educational facilities in Cape Town

OBJECTIVE. To assess the dental needs of a group of children with intellectual disability (ID) attending six special educational facilities in Cape Town, South Africa. METHODS. This was a cross-sectional study based on a convenience sampling method. One hundred and fifty-seven children with ID attending six special educational facilities in Cape Town were included in the survey. Five schools were exclusively funded by the State and one school received additional private financial support. The oral examinations complied with guidelines drafted by Special Olympics Special Smiles programme and the Centers for Disease Control, USA. RESULTS. The most common dental disorders requiring management were gingival disease (69%) and untreated dental caries (68%). Almost 50% of the children had missing teeth. Twenty-nine percent needed orthodontic correction of malocclusion and 7% had structural abnormalities of their teeth that required either aesthetic or functional intervention. Fillings were evident in only 8% of the children. Females required more dental treatment than males. The dental needs of children with ID increased with age. There were no significant differences in the dental needs of children attending State-funded schools and those attending the single school that received additional financial assistance. CONCLUSION. The frequency of unmet dental needs of children with ID attending special educational facilities in Cape Town was high and the dental care available to them was minimal. The study highlights the need for improved dental services to ensure that optimal oral health is accessible to children with ID attending special educational facilities in Cape Town.DHE

Rubinstein-Taybi syndrome:dental manifestations and management

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

Spina bifida: A multidisciplinary perspective on a many-faceted condition

Open spina bifida or myelomeningocele (SBM) is the most common birth defect involving the central nervous system, second only in incidence to congenital cardiac disease. Outcomes in this disorder were poor until the mid-20th century, when modern neurosurgical techniques (closing the lesion and treating hydrocephalus) and treatment for the neuropathic bladder addressed the major causes of mortality, although SBM may still be poorly treated in the developing world. Initial management – or mismanagement – has a profound impact on survival and long-term quality of life

Investigating developmental delay in South Africa: A pragmatic approach

Global developmental delay and intellectual disability are common disorders in every population, with a prevalence of 1 - 5%. Although a specific cause is not always immediately identifiable, for many affected people the aetiology is genetic or the result of secondary insult to the developing brain. Investigating children with intellectual developmental disorders (IDD) may be a significant challenge, especially in resource-limited settings. Comprehensive clinical evaluation is the first step and frequently determines the direction of further investigations. Hearing and vision screening and thyroid function tests should be performed in most patients. Children with neurological findings should undergo brain imaging, and careful consideration should be given to potential metabolic disorders in all children with IDD, a number of whom are amenable to treatment. Most children in whom a specific direction is not suggested after history-taking and examination, should be tested for chromosomal abnormalities, ideally with chromosomal microarray, which has a diagnostic detection rate of 8 - 20% in IDD. Additional tests may be indicated in particular settings, including broad-based testing for single-gene disorders, such as next-generation sequencing gene panels or exome analysis. All genetic testing has the potential of finding variants of uncertain significance, particularly when there are limited population data, such as in Africa. Making a specific diagnosis in IDD is of benefit to patients, their families and society. Therefore, a rational approach to investigating this group of patients is essential to maximise the health benefit in a cost-effective way