Genomic duplication in Dyggve Melchior Clausen syndrome, a novel mutation mechanism in an autosomal recessive disorder.

BACKGROUND: Dyggve Melchior Clausen syndrome (DMC) is a severe autosomal recessive skeletal dysplasia associated with mental retardation. Direct sequencing of genomic DNA has identified causative mutations in the gene Dymeclin (chromosome 18q12-21), with the majority predicting the generation of a truncated protein product. OBJECTIVE: To carry out molecular genetic studies in three DMC kindreds. RESULTS: Two novel nonsense mutations and two complex genomic duplication events resulting in exon repetition were identified. CONCLUSIONS: Exon dosage assessment or mRNA analysis, in addition to direct genomic DNA sequencing, should be employed in the investigation of DMC affected individuals. Genomic duplication may be the causative mutation mechanism in other autosomal recessive disorders.

A new form of hypohidrotic ectodermal dysplasia.

We report on a 17-yr-old young woman with an apparently new tricho-onycho-hypohidrotic ectodermal dysplasia. The manifestations include primary interdigital webbing, contractures of fingers and toes, conjunctivitis from narrowing of nasolacrimal ducts, and a small cortical opacity in the lens of the left eye. Psychosocial problems due to the cosmetic appearance are severe. Cause is uncertain.

Pigmentary abnormalities in trisomy of chromosome 13.

This paper documents an unusual pigmentary mosaicism in a patient with translocation trisomy of chromosome 13. The dermatological lesions include: (1) broad hypopigmented bands following the typical description of Blaschko's lines on the dorsal aspect of both lower limbs; (2) horizontal linear streaks over the spine without the typical central V-shaped dip of Blaschko; and (3) a 'patchwork' hypopigmentation over the face, neck, chest, upper limbs and ventral surface of lower limbs. The lesions in (3) resemble the rare 'phylloid' or leaf-like pigmentary mosaicism type 3 of Happle, but differ in that the pattern shows no midline separation. A translocation trisomy 13 was uniformly detected on peripheral lymphocyte and skin fibroblast cultures from the hypopigmented and normal skin and there was no evidence of cytogenetic mosaicism or chimerism. These lesions resemble those of hypomelanosis of Ito on histopathological assessment.

Genetic disorders in the Indian community of South Africa.

OBJECTIVES: To determine the range of genetic disorders in the Indian population of South Africa, assess relevant historical and demographical factors, and discuss the implications for medical and genetic care. METHODS: WSW reviewed the archived data pertaining to patients seen in his paediatric practice in Durban during the past 45 years. Likewise, PB reviewed case details of persons encountered since 1972 in Cape Town, at outreach clinics, and in special institutions for the handicapped throughout South Africa. Additional information was accessed through the Cape Genetic Heritage archive. RESULTS: In addition to the common ubiquitous worldwide genetic disorders, several rare heritable conditions are present in the Indian community of South Africa. These disorders are the consequence of the founder effect and reflect the biological heritage of the early immigrants. Demographic factors (notably endogamy) are also relevant in this respect. As a result of these processes, thalassaemia is by far the most common and important genetic disorder in the Indian population in the country. CONCLUSION: Awareness of the presence of specific genetic conditions in the Indian community of South Africa is important in the diagnostic process. In turn, diagnostic precision facilitates accurate prognostication and optimal medical and genetic management.

Epidermolysis bullosa misdiagnosed as child abuse. A report of 3 cases.

Three cases of epidermolysis bullosa are reported; the typical skin lesions were misdiagnosed as non-accidental injury to the children. Awareness of the manifestations of this uncommon genodermatosis, as well as the wearing of identifying Medic Alert discs, should prevent this inappropriate diagnostic stigmatization.

The Dyggve-Melchior-Clausen syndrome in Indian siblings.

The clinical and radiographic features of a brother and sister with the Dyggve-Melchior-Clausen syndrome are presented. These features differentiate this syndrome from other bone dysplasias causing short trunk dwarfism. In addition to the vertebral, pelvic and proximal limb defects typical of this syndrome, both these patients have more severe distal limb involvement than has been described previously. Their parents are first cousins and have four other unaffected children, which supports an autosomal recessive mode of inheritance for this syndrome. The ancestors of this kindred emigrated to South Africa from India in the 19th century.

Safety restraints for children travelling in motor vehicles.

The parents of 202 children were questioned about their use of safety restraints for their children while they were passengers in a motor vehicle. The result of the survey shows a low incidence of use of safety restraints by both parents and their children and that the type used for children was, in the majority of cases, both inadequate and dangerous. There was a correlation between the use of safety restraints by both parent and child on the day of questioning, but no association was found between the use of these restraints and the social class, educational standard achieved, income group, home language or home province of the parents. Neither was there any association between the use of safety restraints and a history of previous traffic accidents which had involved the family or close friends. In South Africa, the number of deaths in childhood as a result of motor vehicle accidents exceed those from the same cause in the United Kingdom. We consider that the medical profession in this country should inform the public of the desirability of fitting and using safety restraints of the correct type for children while they are passengers in motor vehicles. Reasons for the high incidence of serious injuries to children who are passengers in motor vehicles are reviewed and the methods of restraining children of different ages are discussed.

Weaver's syndrome--primordial excessive growth velocity. A case report.

We report on a black child with the Weaver syndrome of primordial overgrowth, the seventh and largest case thereof yet recorded. His birth weight was 10 200 g and he has continued to grow at an excessive velocity. At the age of 14 months his weight was 30 kg, his height 105 cm and his radiological bone age between 6 and 7 years. Other features which conform to previous reports are a peculiar face with a long philtrum, protuberant lower lip, relative micrognathia, large dysplastic ears, excessive loose skin folds around the scalp, neck and trunk, large hands with camptodactyly, varus deformities of the feet and a hoarse, low-pitched voice. A significant feature in this patient is lumbar kyphosis due to hypoplasia of the second and third lumbar vertebrae. Biochemical and endocrinological tests did not reveal an abnormality.

Nephrogenic diabetes insipidus presenting with infantile hypotonia. A report of 2 cases.

Nephrogenic diabetes insipidus usually presents with polyuria, polydipsia, fever, vomiting, dehydration and failure to thrive. However, in infancy polyuria may be absent because of dehydration and reduced glomerular filtration rate. In 2 cases the main presenting feature was hypotonia, with marked head lag. Family studies confirmed the X-linked mode of inheritance of the disease; in case 1 the disease appeared to have arisen as a new mutation in the mother, and in case 2 the carrier status was traced back to the great-grandmother. Pitfalls in the diagnosis and detection of the carriers are discussed. Treatment with thiazide diuretics and prostaglandin synthesis inhibitors is effective in reducing urine volumes and polydipsia. The early detection of the disease and adequate management may prevent such complications as megacystis, mega-ureter and hydronephrosis, with resulting renal failure. Mental and physical retardation may also be avoided.

Biliary atresia in a twin.

The occurrence of biliary atresia in one of a pair of male twins is reported. The current concepts regarding the aetiology of biliary atresia are examined in relation to this case; and neither the concept of a transplacental agent nor that of a genetic trigger mechanism seems probable. It is concluded that, as with many congenital defects, biliary atresia is probably the end-result of different aetiological factors, among which viruses and other agents may cross the placenta to cause it, whether or not there is a genetic predisposition in the individual fetus, or the biliary system may simply fail to develop.

Neonatal septicaemia due to a nutritionally deficient streptococcus. A case report.

A case of neonatal septicaemia due to a nutritionally deficient streptococcus is described. Unusual features were abdominal distension and excessive nasogastric aspirate with infrequent stools. Recovery followed treatment with intravenous penicillin and gentamicin. Attention is drawn to the possibility of missing such infections unless culture media are supplemented with vitamin B in cases in which staining of the blood culture reveals Gram-positive cocci which fail to grow on standard plates.

Prenatal ultrasonographic diagnosis and successful management of mediastinal teratoma. A case report.

A case of mediastinal teratoma, diagnosed in utero by realtime ultrasonography during a late 3rd trimester evaluation of polyhydramnios, is described. Prompt respiratory assistance to the infant at birth and early surgical intervention led to a successful outcome.

Examination of sexually abused children.

The approach to the examination of sexually abused children differs from that of normal for sick children and also from that of adults who have been the victims of rape. While the physical and psychological welfare of the patient must be the prime concern, medico-legal aspects are equally important. In the interests of the patient the initial examination and subsequent management and follow-up should be done by those with specific skills and with the support of members of disciplines essential to the total management of the complex and not uncommon problem of sexual abuse in children.

Prader-Willi syndrome in South African patients--clinical and molecular diagnosis.

STUDY OBJECTIVE: To assess clinically South African patients with the putative diagnosis of Prader-Willi syndrome (PWS) and confirm this diagnosis by DNA/molecular analysis. DESIGN: Prospective, nationally based, combined clinical and laboratory study. MAIN RESULTS: Thirty-seven patients with a putative diagnosis of PWS were examined by clinical geneticists. Only 13 (35.1%) of these patients had the diagnosis of PWS confirmed by molecular analysis, and all 13 PWS patients had positive scores using the PWS consensus diagnostic criteria of Holm et al. The clinical features of the remaining 24 (64.9%) non-PWS patients were analysed and 23 did not have the neonatal, infantile and childhood features necessary to warrant consideration of a diagnosis of PWS; neither did they obtain a positive score according to Holm et al.'s criteria. CONCLUSION: PWS was confirmed in only 35% of South African patients with a putative PWS diagnosis, confirming that this condition is overdiagnosed and that the clinical diagnosis is difficult. Clinically, the diagnostic criteria of Holm et al. are of great assistance in making the diagnosis, but it remains essential to confirm the diagnosis by molecular analysis.