Medical genetics in primary health care.
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Community Health Services↗
Biomedical subjects
D Viljoen
Publications and source records attributed to D Viljoen.
Aplasia cutis congenita with epibulbar dermoids: further evidence for syndromic identity of the ocular ectodermal syndrome.
We have investigated 2 young South African girls with aplasia cutis congenita, epibulbar dermoids, and strabismus. This unique association of anomalies was first documented in two unrelated boys by Toriello et al. [1993: Am. J. Med. Genet. 45:764-766]. Our clinical and histological findings are markedly similar, and we think this to be the second report of individuals with this rare syndrome.
Adult↗
Congenital contractural arachnodactyly (Beals syndrome).
Congenital contractural arachnodactyly (CCA) is an autosomal dominant disorder akin to, but usually less severe than, Marfan syndrome. The clinical features are marfanoid habitus, arachnodactyly, crumpled ears, camptodactyly of the fingers and adducted thumbs, mild contractures of the elbows, knees, and hips, and mild muscle hypoplasia especially of the calf muscles. Many patients have kyphoscoliosis and mitral valve prolapse and, very occasionally, aortic root dilatation and ectopia lentis have been described. Linkage to a gene coding for fibrillin on chromosome 5q23-31 has been shown in several kindreds. The prognosis for a normal lifespan is good and improvement in joint contractures is usual.
Abnormalities, Multiple↗
Duchenne and Becker muscular dystrophy prevalence in South Africa and molecular findings in 128 persons affected.
A genetic service for Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) was initiated in Cape Town in 1987. Of the 143 DMD patients diagnosed during the period 1987-1992, 66 had a familial pattern of inheritance and 77 were apparently sporadic. Twenty BMD patients were identified, of whom 12 had other affected relatives and 8 were sporadic. Overall minimum prevalence rates of 1/100,000 for DMD and 1/755,000 for BMD were calculated. A markedly low DMD prevalence in the indigenous black population (1/250,000) contributed to the overall low DMD prevalence in South Africa when compared with that in the UK (1/40,000). By means of molecular methods, the diagnosis in 42% of the affected DMD males was confirmed by detection of deletions in the dystrophin gene. Deletions were identified in 50% of Indian, white and mixed ancestry patients. In contrast, only 22% of blacks had identifiable deletions. DMD appears to be underrepresented in the black population; the low deletion frequency in this group suggests that unique mutations not detectable by methods used in this study may be more frequent in these patients than in the other populations. The increased DMD frequency in Indians corroborates findings reported from the UK.
Chromosome Deletion↗
Brachydactylous dwarfs of Mseleni.
Eight individuals with an unusual dwarfing skeletal dysplasia have been investigated in a remote rural area in Northern Zululand, South Africa. These dwarfed individuals are members of a community numbering some 10,000 persons; approximately 20% have a degenerative arthropathy affecting mainly the major joints of the hips, knees, ankles, and spine. The pathogenesis of the latter disorder, which is known as Mseleni joint disease (MJD), remains obscure. The dwarfed persons have some radiological findings in keeping with MJD, but they are, in addition, of short stature and have marked brachydactyly of their fingers and toes. The pathogenetic relationship between these conditions, if any, is unclear but may have important implications for their causal elucidation.
Adult↗
Osteogenesis imperfecta type III: mutations in the type I collagen structural genes, COL1A1 and COL1A2, are not necessarily responsible.
Most forms of osteogenesis imperfecta are caused by dominant mutations in either of the two genes, COL1A1 and COL1A2, that encode the pro alpha 1(I) and pro alpha 2(I) chains of type I collagen, respectively. However, a severe, autosomal recessive form of OI type III with a comparatively high frequency has been recognised in the black populations of southern Africa. We preformed linkage analyses in eight OI type III families using RFLPs associated with the COL1A1 and COL1A2 loci to determine whether mutations in the genes for type I collagen were responsible for this form of OI. Recombination between the OI phenotype and polymorphic markers at both loci was shown in three of the eight families investigated. The combined lod scores for the eight families were -10.6 for COL1A1 and -11.2 for COL1A2. Further, we examined the type I procollagen produced by skin fibroblast cultures derived from 15 affected and 12 unaffected subjects from the above eight families plus one further family. We found no evidence for defects in the synthesis, structure, secretion, or post-translational modification of the chains of type I procollagen produced by any of the family members. These results suggest that mutations within or near the type I collagen structural genes are not responsible for this form of OI.
Africa, Southern↗
Molecular investigation of familial Beckwith-Wiedemann syndrome: a model for paternal imprinting.
In familial Beckwith-Wiedemann syndrome (BWS), the mode of inheritance is uncertain and possible patterns include autosomal dominant, multifactorial and autosomal dominant sex-dependent inheritance. Genomic imprinting has recently been invoked to explain the unusual inheritance patterns in several disorders. We have previously reviewed 28 published kindreds of BWS and shown that paternal imprinting is probably responsible for familial BWS. In the present paper, highly informative RFLP markers in the 11p15.5 region have been shown to segregate with the disease gene as an autosomal dominant, but phenotypic manifestations in an offspring are dependent on the sex of the parent contributing the defective gene. In contrast to previous reports in which imprinting of the growth stimulator gene, IGF2, has been invoked as the mechanism explaining sporadic cases of BWS (especially in situations where uniparental disomy and trisomy of the 11p15.5 region has occurred), it is suggested that paternal imprinting of a growth suppressor gene, e.g., H19, may be one of the causes of familial BWS.
Alleles↗
Developmental anomalies in monozygous twins resembling the human homologue of the mouse mutant disorganization.
Human monozygous (Mz) twins are described with a pattern of abnormalities similar to those reported in heterozygous expression of the mouse mutant disorganisation gene (Ds). These include anomalies of the skeletal, gastrointestinal, genito-urinary and central nervous system. Concordance in Mz twins is suggestive of a genetic aetiology and lends further credence to the putative existence of a human homologue for Ds.
Abnormalities, Multiple↗
Ehlers Danlos syndrome type VIIB. Incomplete cleavage of abnormal type I procollagen by N-proteinase in vitro results in the formation of copolymers of collagen and partially cleaved pNcollagen that are near circular in cross-section.
We have shown that a child with Ehlers Danlos syndrome (EDS) type VII has a G to A transition at the first nucleotide of intron 6 in one of her COL1A2 alleles. Half of the cDNA clones prepared from the proband's pro alpha 2(I) mRNA lacked exon 6. The type I procollagen secreted by the proband's dermal fibroblasts in culture was purified, and collagen fibrils were generated in vitro by cleavage of the procollagen with the procollagen N- and C-proteinases. Incubation of the procollagen with N-proteinase resulted in a 1:1 mixture of pCcollagen and uncleaved procollagen. Incubation of this mixture with C-proteinase generated collagen and abnormal pNcollagen (pNcollagen-ex6) that readily copolymerized into fibrils. By electron microscopy these fibrils resembled the hieroglyphic fibrils seen in the N-proteinase-deficient skin of dermatosparactic animals and humans and were distinct from the near circular cross-section fibrils seen in the tissues of individuals with EDS type VII. Further incubation of the hieroglyphic fibrils with N-proteinase resulted in partial cleavage of the pNcollagen-ex6 in which the abnormal pN alpha 2(I) chains remained intact. These fibrils were not hieroglyphic but were near circular in cross-section. Fibrils formed from collagen and pNcollagen-ex6 that had been partially cleaved with elevated amounts of N-proteinase prior to fibril formation were also near circular in cross-section. The results are consistent with a model of collagen fibril formation in which the intact N-propeptides are located exclusively at the surface of the hieroglyphic fibrils. Partial cleavage of the pNcollagen-ex6 by N-proteinase allows the N-propeptides to be incorporated within the body of the fibrils. The model provides an explanation for the morphology and molecular composition of collagen fibrils in the tissues of patients with EDS type VII.
Amino Acid Sequence↗
Schwartz-Jampel syndrome (chondrodystrophic myotonia).
Schwartz-Jampel syndrome is a rare autosomal recessive disorder. Joint contractures, generalised myotonia, skeletal anomalies, and facial dysmorphism are common features; malignant hyperthermia is a potentially lethal complication during anaesthesia.
Adult↗
Evidence for paternal imprinting in familial Beckwith-Wiedemann syndrome.
A previously unreported family in which seven members in two generations have Beckwith-Wiedemann syndrome (BWS) is documented. Paternal imprinting of the gene responsible for BWS is involved as the mechanism responsible for the aberrant inheritance pattern in this kindred. A review of published reports showed 27 previously published pedigrees with two or more affected subjects with BWS. Paternal imprinting would explain the non-mendelian inheritance of BWS in all but four kindreds. The latter families are examined in more detail and in only one example is the evidence against imprinting totally unexplained.
Beckwith-Wiedemann Syndrome↗
Pseudoxanthoma elasticum: similar autosomal recessive subtype in Belgian and Afrikaner families.
A multidisciplinary survey of the clinical and genetic characteristics of 26 Belgian and 32 Afrikaner families with biopsy-proven pseudoxanthoma elasticum (PXE) was undertaken. The major PXE phenotype emerging from this study is very similar in both patient groups and is characterized by severe ophthalmologic manifestations with variable, mild cutaneous and vascular symptoms. In the families with more than one affected relative, segregation analysis is compatible with autosomal recessive inheritance in both groups. It is suggested that the PXE phenotype of these Belgian and Afrikaner patients is distinct from the other recognized PXE subtypes. The phenotypic resemblance in both patient groups raises the question whether a similar genetic mechanism is involved.
Adult↗
Epiphyseal stippling in acrodysostosis.
Widespread epiphyseal stippling was demonstrated radiologically during the early months of life in 7 children with acrodysostosis. This finding, which does not seem to have been previously documented in this disorder, is important in the differential diagnosis.
Bone Diseases, Developmental↗
Dietary manipulation for treating infants with prolonged dehydrating diarrhoea: a comparison of four different formulae.
Dietary manipulation is often the first step in the treatment of infants with persistent acute dehydrating diarrhoea. This usually entails elimination of lactose, but other disaccharides or whole protein may be causing the disease. Serial elimination of these takes time and it may be preferable to use a whole protein and disaccharide-free formula as the first feed change. This study assessed the effect on stool weight of a change from cow's milk formula feeds to one of four different formulae in infants with severe diarrhoea persisting after 3 days in hospital. Two feeds were lactose-free soy formulae containing sucrose, one was disaccharide-free soy formula and one a disaccharide-free protein hydrolysate. Regardless of which feed the infants received, diarrhoea resolved in approximately 50% following the change in diet. Comparing those who got better with those who did not, the former were generally better nourished and had an initial lower stool output, but it was impossible to predict on clinical grounds which individual would respond to the removal of cow's milk. The results suggest that elimination of lactose in infants with persistent severe diarrhoea will benefit a significant number in the early stage of the disease. As there is no additional benefit from eliminating sucrose or whole protein at this stage, the cheapest available lactose-free formula should be used initially.
Diarrhea, Infantile↗
Beals syndrome: clinical and molecular investigations in a kindred of Indian descent.
Eight members of a 3-generation kindred of Indian descent with congenital contractural arachnodactyly (Beals syndrome) have been appraised. Considerable variation was noted in the clinical features of affected persons, and the previously unreported associated finding of clubbing of the fingers and toes was evident in two individuals. The family was investigated using conventional serum and protein markers, and RFLP probes for type I and II collagen. No linkage in affected members could be demonstrated with type I collagen probes.
Adolescent↗
Hearing impairment and pigmentary disturbance.
Hearing impairment is a variable manifestation of several heritable conditions in which pigmentation of the skin or eyes is abnormal. Some of these disorders are well recognized although uncommon, while others are virtually private syndromes. Practical issues concerning the major conditions of this type are reviewed in this article on a basis of a survey of 4452 profoundly deaf children attending special schools in Southern Africa, together with investigations in affected families. The Waardenburg syndrome (WS), which is the most common deafness-depigmentation disorder, was present in 121 (2.7%) of the 4452 deaf scholars. Further studies in 7 multigeneration affected families confirmed phenotypic variability and indicated a need for internationally agreed diagnostic criteria. In 4 Cape Town families of mixed ancestry the WS-I gene was linked to the 2q37 locus, but in another large kindred no linkage could be demonstrated. Nonallelic heterogeneity is possible. There is uncertainty concerning possible interrelationship between WS and piebaldism. The phenotypic consistency of a South African family in which 7 persons in 3 generations had gross piebaldism in the absence of disturbance of hearing or involvement of the eyes and periorbital structures is suggestive that this disorder and WS are separate entities. Molecular investigations indicate that the gene for piebaldism in this kindred is not situated at the WS-I locus 2q37. Deafness and hyperpigmentation are present in neurofibromatosis type II (acoustic neuromata) and the multiple lentigines syndrome, while retinal pigmentation is a feature of the Usher syndrome. This latter entity is apparently much less common in Southern Africa than in other parts of the world.
Albinism↗
Profound childhood deafness in southern Africa.
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Africa, Southern↗
Marfan syndrome: a diagnostic dilemma.
During a 17-year period (1971-1988), the Marfan syndrome was diagnosed in 66 patients seen through the Department of Human Genetics, Medical School, University of Cape Town. Following reappraisal and application of the Pyeritz criteria, this diagnosis was confirmed in 33. Of the others, 17 with tall stature and a Marfanoid habitus had insufficient additional manifestations for firm diagnosis and were eliminated from the series. Sixteen had Marfanoid habitus, tall stature, arachnodactyly and other abnormalities which might have indicated the presence of a different syndrome. The difficulty in making a clinical diagnosis of the Marfan syndrome is stressed and emphasizes the need for a biomolecular marker.
Adolescent↗