Pyle metaphyseal dysplasia in an African child: Case report and review of the literature

Pyle disease (OMIM 265900), also known as metaphyseal dysplasia, is a rare autosomal recessive disorder with no known gene mutation. We report a case of Pyle disease in a 7-year-old African boy of mixed ancestry who presented with finger and wrist fractures following minor trauma. The radiological findings revealed abnormally broad metaphyses of the tubular bones, known as Erlenmeyer-flask bone deformity, and mild cranial sclerosis, both hallmarks of the condition. We report the first case in a patient with African ancestry, which could help in the gene discovery of this rare autosomal recessive skeletal dysplasia with unknown mutations.DHE

Parental access to hospitalised children during infectious disease pandemics such as COVID-19

The COVID-19 pandemic has resulted in many hospitals severely limiting or denying parents access to their hospitalised children. This article provides guidance for hospital managers, healthcare staff, district-level managers and provincial managers on parental access to hospitalised children during a pandemic such as COVID-19. It: (i) summarises legal and ethical issues around parental visitation rights; (ii) highlights four guiding principles; (iii) provides 10 practical recommendations to facilitate safe parental access to hospitalised children; (iv) highlights additional considerations if the mother is COVID-19-positive; and (v) provides considerations for fathers. In summary, it is a child’s right to have access to his or her parents during hospitalisation, and parents should have access to their hospitalised children; during an infectious disease pandemic such as COVID-19, there is a responsibility to ensure that parental visitation is implemented in a reasonable and safe manner. Separation should only occur in exceptional circumstances, e.g. if adequate in-hospital facilities do not exist to jointly accommodate the parent/caregiver and the newborn/infant/child. Both parents should be allowed access to hospitalised children, under strict infection prevention and control (IPC) measures and with implementation of non-pharmaceutical interventions (NPIs), including handwashing/sanitisation, face masks and physical distancing. Newborns/infants and their parents/caregivers have a reasonably high likelihood of having similar COVID-19 status, and should be managed as a dyad rather than as individuals. Every hospital should provide lodger/boarder facilities for mothers who are COVID-19-positive, COVID-19-negative or persons under investigation (PUI), separately, with stringent IPC measures and NPIs. If facilities are limited, breastfeeding mothers should be prioritised, in the following order: (i) COVID-19-negative; (ii) COVID-19 PUI; and (iii) COVID-19-positive. Breastfeeding, or breastmilk feeding, should be promoted, supported and protected, and skin-to-skin care of newborns with the mother/caregiver (with IPC measures) should be discussed and practised as far as possible. Surgical masks should be provided to all parents/caregivers and replaced daily throughout the hospital stay. Parents should be referred to social services and local community resources to ensure that multidisciplinary support is provided. Hospitals should develop individual-level policies and share these with staff and parents. Additionally, hospitals should ideally track the effect of parental visitation rights on hospital-based COVID-19 outbreaks, the mental health of hospitalised children, and their rate of recovery.South African Medical Research Councilhttp://www.samj.org.zaPaediatrics and Child Healt

Masking through averages - intraprovincial heterogeneity in HIV prevalence within the Western Cape

CITATION: Shaikh, N., et al. 2006. Masking through averages - intraprovincial heterogeneity in HIV prevalence within the Western Cape. South African Medical Journal, 96(6):538-543.The original publication is available at http://www.samj.org.zaObjective. To measure HIV prevalence at health-district level in the Western Cape (WC) and to compare these findings with those of the National HIV Antenatal Surveys (NHASs). This investigation aimed to estimate the degree of heterogeneity of HIV prevalence within the province in order to inform the design of appropriate and targeted HIV interventions. Method. Annual cross-sectional, unlinked district HIV antenatal surveys were implemented in all 25 health districts of the WC for the years 2001 - 2004, concurrently with the NHAS. A stratified proportional sample was drawn for each district, involving all 344 antenatal clinics in the province, and the anonymous screening method as described by the World Health Organization (WHO) was applied. Results. The NHAS revealed a significant increase in HIV prevalence in the WC from 8.6% (95% confidence interval (CI): 5.6 - 11.6) in 2001 to 15.4% (95% CI: 12.5 - 18.2) in 2004. The district-level HIV surveys showed wide variation in HIV prevalence across the health districts, which increased progressively during this period (a range of 0.6 - 22% for the year 2001 increased to 1 - 33% in 2004). Spatial analysis of HIV prevalence by health district for this period also revealed progressive spatial growth of the sub-epidemics, with the highest prevalence observed in districts located in the Cape metropole region. Conclusions. These concurrent surveys highlight the fact that examining a provincial estimate of HIV prevalence alone has the potential to mask epicentres within the province. This underscores the importance of expanding the surveillance systems to detect heterogeneity sub-provincially, in order to link with local-level planning and resource allocation.http://www.samj.org.za/index.php/samj/article/view/1136Publisher’s versio

Sequencing of GJB2 in Cameroonians and Black South Africans and comparison to 1000 Genomes Project Data Support Need to Revise Strategy for Discovery of Nonsyndromic Deafness Genes in Africans

Mutations in the GJB2 gene, encoding connexin 26, could account for 50% of congenital, nonsyndromic, recessive deafness cases in some Caucasian/Asian populations. There is a scarcity of published data in subSaharan Africans. We Sanger sequenced the coding region of the GJB2 gene in 205 Cameroonian and Xhosa South Africans with congenital, nonsyndromic deafness; and performed bioinformatic analysis of variations in the GJB2 gene, incorporating data from the 1000 Genomes Project. Amongst Cameroonian patients, 26.1% were familial. The majority of patients (70%) suffered from sensorineural hearing loss. Ten GJB2 genetic variants were detected by sequencing. A previously reported pathogenic mutation, g.3741_3743delTTC (p.F142del), and a putative pathogenic mutation, g.3816G > A (p.V167M), were identified in single heterozygous samples. Amongst eight the remaining variants, two novel variants, g.3318-41G > A and g.3332G > A, were reported. There were no statistically significant differences in allele frequencies between cases and controls. Principal Components Analyses differentiated between Africans, Asians, and Europeans, but only explained 40% of the variation. The present study is the first to compare African GJB2 sequences with the data from the 1000 Genomes Project and have revealed the low variation between population groups. This finding has emphasized the hypothesis that the prevalence of mutations in GJB2 in nonsyndromic deafness amongst European and Asian populations is due to founder effects arising after these individuals migrated out of Africa, and not to a putative ‘‘protective’’ variant in the genomic structure of GJB2 in Africans. Our results confirm that mutations in GJB2 are not associated with nonsyndromic deafness in Africans.Jason Bosch, Jean Jacques N. Noubiap, Collet Dandara, Nomlindo Makubalo, Galen Wright, Jean-Baka Domelevo Entfellner, Nicki Tiffin, Ambroise Wonka

No evidence for clinical utility in investigating the connexin genes GJB2, GJB6 and GJA1 in non-syndromic hearing loss in black Africans

Background. Deafness is the most common sensory disability in the world. Globally, mutations in GJB2 (connexin 26) have been shown to play a major role in non-syndromic deafness. Two other connexin genes, GJB6 (connexin 30) and GJA1 (connexin 43), have been implicated in hearing loss, but these genes have seldom been investigated in black Africans. We aimed to validate the utility of testing for GJB2, GJB6 and GJA1 in an African context.Methods. Two hundred and five patients with non-syndromic deafness from Cameroon and South Africa had the full coding regions of GJB2 sequenced. Subsequently, a carefully selected subset of 100 patients was further sequenced for GJB6 and GJA1 using Sanger cycle sequencing. In addition, the large-scale GJB6-D3S1830 deletion was investigated.Results. No pathogenic mutations that could explain the hearing loss were detected in GJB2, GJB6 or GJA1, and the GJB6-D3S1830 deletion was not detected. There were no statistically significant differences in genomic variations in these genes between patients and controls. A comprehensive literature review supported these findings.Conclusion. Mutations in GJB2, GJB6 and GJA1 are not a major cause of non-syndromic deafness in black Africans and should not be investigated routinely in clinical practice