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This article focuses on a cytogenetic survey of a mentally retarded school-age population with special reference to fragile sites. The population to be studied was selected as described previously. The school medical records of all the boys at the educationally subnormal (severe) schoolboys (ESN(S)) schools in Walsall; North, South East and Central Warwickshire; and of all the girls and boys at ESN(S) and educationally subnormal (moderate) schoolboys (ESN(M)) schools in Coventry were examined. The parents of the children with apparently idiopathic mental retardation were sent a letter seeking permission for an examination and venepuncture for cytogenetic analysis. A note was made of their birth weight, history of epilepsy and early medical history from the school medical records. The IQ was assessed for each child. A Vineland Social Maturity Scale was filled in for each child at the ESN(S) school by his class teacher. The probands consisted of 443 mentally handicapped schoolchildren. Parental agreement was high among the ESN(S) children but lower among those with moderate handicap.

Over a ten year period of running a joint ophthalmological/genetic clinic, 387 index patients were advised, and a further 260 individuals (relatives of the above) were examined and counselled. Determination of the precise diagnoses and modes of inheritance in the index patients necessitated retinal function tests in 267 (69%) and examination of 84 of their parents and 23 sisters and daughters. Finally, 41% of index patients and 39% of their relatives were given high risks for transmitting an autosomal dominant or X-linked disorder to their children. It is noteworthy that 16% of these high-risk index patients and 66% of these high-risk relatives had no visual symptoms; ophthalmological expertise was-required to assess the significance of their minor signs. It was concluded that an active Register is required for contacting relatives outside the nuclear family, and for future recall of children currently too young for carrier tests or genetic counselling. [ABSTRACT FROM AUTHOR]

Clinical observations were made on a series of 156 boys with severe mental retardation, before cytogenetic results were known. The clinical features that helped to distinguish the 14 boys with the fragile X chromosome from those without were: head circumference over the 50th centile, postpubertal testicular volume over the 50th centile, and an IQ between 35 and 70. If the above clinical features were all present, then the chance of finding the fragile X chromosome was 1 in 3.6, whereas the chance of finding this abnormality in any boy with severe idiopathic mental retardation, regardless of his clinical features, was 1 in 9. Two boys with fragile X syndrome did not, however, possess any of the above clinical features. Moreover, some of the other retarded boys had clinical features of the syndrome, or an X linked pedigree, but lacked the chromosome abnormality. [ABSTRACT FROM AUTHOR]

A genetic study of children attending ESN(M) schools in Coventry has shown a recurrence risk of idiopathic mental retardation in sibs lying between 1 in 4 and 1 in 5. There was also a prevalence of mental retardation in other relatives that was greater than the population prevalence, and was less for second degree relatives than for first degree, and less still for third degree relatives. Recurrence in sibs was greater if more than one first degree relative was affected. There was no suggestion of a contribution by X linked genes, once the fragile X syndrome had been excluded. The presence of perinatal and other environmental factors in the index children did not alter the recurrence risk for sibs except for very low birth weight. There was a low recurrence rate of mental retardation in Asian families, suggesting that they had a different distribution of intelligence from non-Asian families. [ABSTRACT FROM PUBLISHER]

We have analysed over 300 patients suffering from Duchenne or Becker muscular dystrophy (DMD or BMD). Deletions have been characterised which encompass either the pERT87 (DXS164) locus only, the XJ1.1 (DXS206) and HIP25 loci only, or all three loci. These loci have been shown to lie within the DMD region covering several hundred kilobases (kb) of DNA. One mildly affected BMD patient possesses a deletion of at least 110 kb including exons of the DMD gene. Other patients with similar exon deletions, or smaller deletions, show the more severe phenotype typical of DMD. We conclude from these studies that the severity of the clinical phenotype cannot be explained on the basis of the size of the deletion. We discuss this in the context of candidate gene sequences. [ABSTRACT FROM PUBLISHER]

A population study has been carried out among schoolchildren in the City of Coventry in order to ascertain the frequency of mental retardation associated with the fragile X chromosome. The prevalence of the fragile X mental retardation syndrome in the 11 to 16 year age group (the age of greatest ascertainment) was about 1.0 per 1,000 and therefore indicates that the syndrome is a major cause of mental retardation. [ABSTRACT FROM PUBLISHER]

This paper describes a community based study of 156 boys with idiopathic, severe mental retardation. The boys were examined and a pedigree taken before the cytogenetic results were known. The prevalence of the fragile X chromosome among this group of boys was high: 9% in the whole group and 11% after 39 boys with specific features had been excluded. The fragile X syndrome is therefore an important cause of idiopathic, severe retardation. Its clinical features of large head, large testes, and IQ in the 35 to 70 range were often but not always present in the 14 boys identified in this study. In the whole group, the recurrence of severe mental subnormality was high: 1 in 8 for brothers and 1 in 25 for sisters. This high recurrence was partly due to the fragile X syndrome, partly to X linked mental retardation not accompanied by cytogenetic abnormalities, and partly due to autosomal recessive disease. Autosomal recessive disease was perhaps higher in the West Midlands than elsewhere (such as British Columbia, for example 1) because of the disproportionate contribution by Asian immigrants. [ABSTRACT FROM PUBLISHER]

Chromosome analysis using conventional staining, G banding, and, after BUdR incorporation, two R banding methods, one using Hoechst and one acridine orange, were performed on lymphocytes from a pair of female monozygotic twins. The culture conditions were designed to show the presence of the fragile X (q27-28) which had previously been found to be segregating in the family. One twin was of higher than normal intelligence and the other had been diagnosed as mentally retarded. The frequency of the occurrence of the early/active fragile X compared to the overall total of informative fragile X was determined using both methods described above and was also compared with previous published data in the form of a graph showing percentage of early/active fragile X against intelligence. [ABSTRACT FROM PUBLISHER]

This is a study of 138 index patients with retinitis pigmentosa (RP) and their families, in which the selection of index patients was solely on the basis of their residence in Birmingham. Clinical analysis showed that severe disease was as likely to indicate dominant or non-genetic RP as to indicate recessive disease, and that each of three genetic types of uncomplicated RP could probably be divided into two entities. Autosomal dominant RP accounted for at least 22% of index patients but this was likely to be an underestimate because of the low penetrance of the disease. Autosomal recessive disease accounted for not more than 10% of index patients and its rarity was indicated by a high consanguinity rate. Recognisable X linked disease occurred in about 14% of index patients, a similar figure to other studies. The 37% of patients with uncomplicated RP and no obviously affected relative have either autosomal dominant RP or non-genetic RP; it is difficult to know the relative proportions of each. The risks for descendants of patients with recessive disease are clear. The risks of symptomatic RP in the offspring of patients who do, or who might have, dominant RP range from 1 in 2 to 1 in 37 according to the family history and the severity of the RP. [ABSTRACT FROM PUBLISHER]

Using multiple sources, an attempt was made to ascertain all symptomatic cases of retinitis pigmentosa living in the City of Birmingham in June 1978. These methods revealed a prevalence for all ages of 1 in 4869 and a prevalence in the age group 45 to 64 years of 1 in 3195. There was a higher prevalence than expected among young Muslims with consanguineous parents. However, the most accurate prevalence of uncomplicated retinitis pigmentosa among adults was considered to be that found in an outpatient clinic serving adult diabetics, namely, six patients in a clinic population of 8000 to 10 000. [ABSTRACT FROM PUBLISHER]

In a study of 35 index patients who developed myotonic dystrophy between birth and 30 years (neonatal cases aware excluded), 30 could be categorised into two clinical types. The 13 type 1 patients had a more severe limb weakness, of patchy distribution, associated with proportional facial weakness. The 17 type 2 patients had a milder and more diffuse limb weakness; their facial weakness, however, was very pronounced and preceded the limb weakness by several years. All but one of the 25 affected relatives who were examined belonged to the same category as their index relative, providing evidence that the cause of the clinical heterogeneity was genetic. Subsequent observations showed that mental retardation, male infertility, and neonatally affected offspring were commoner in type 2 patients. Congenital myotonic dystrophy could occur among the offspring of either affected males or affected females, but neonatal symptoms were confined to the offspring of affected women. The overall risk for having neonatally affected offspring for this prospective study of young adult patients was 7 in 38, and for the offspring of affected females 7 in 27. The risk for having a surviving child whose mental or physical handicap or both required special schooling was 1 in 12 for males and 4 in 27 for females. [ABSTRACT FROM PUBLISHER]

The segregation of chromosomes 13 distinguishable by Q band fluorescent polymorphisms has been studied in three families with retinoblastoma. The recombination fraction for two of these families and four families previously reported did not differ significantly from 50%. Since a high recombination fraction has been predicted from chiasma frequency between the centromere of chromosome 13 and 13q14 these results neither confirm nor refute the location of the autosomal dominant gene predisposing to retinoblastoma in 13q14. The use of fluorescent markers is not suitable for early recognition of gene carriers in families with retinoblastoma. [ABSTRACT FROM PUBLISHER]

The main purpose of this study was to see if the offspring of surviving neuroblastoma, ganglioneuroblastoma, or ganglioneuroma patients have themselves a risk for developing tumours. No such risk was found. There was a total of 45 liveborn children who were all healthy. These children have passed through about 37 lifetimes of risk for developing neuroblastoma and about six lifetimes of risk for developing ganglioneuroma. No excess of cancers was found among parents and sibs. It was interesting that there was a large female excess (35:12) among these survivors. One factor which may give rise to a better prognosis in females is the tendency of their tumours to mature to benign forms. [ABSTRACT FROM PUBLISHER]

A study of Duchenne muscular dystrophy has shown an approximate prevalence of the disease among schoolboys to be 1 in 4000. Fifty-four families were available for genetic studies. In 19 families there were further affected cases and in 34 families the index patients was an isolated case. The proportion of affected brothers was 0.22 (11 of 50). There were 142 female relatives who had a risk of 1 in 10 or worse of being carriers: 66 of these were aged under 16. As genetic counselling is being increasingly requested by these families, and expansion of genetic services is envisaged. A genetic register, with frequent contact with families by ancillary staff, similar to that in Edinburgh, is considered desirable for the West Midlands. [ABSTRACT FROM PUBLISHER]

In order to obtain control values for the diagnosis of carriers of Duchenne muscular dystrophy, creatine kinase (CK) estimations were performed in two laboratories on 148 healthy teenage girls (of whom 38 were premenarchal and 110 postmenarchal), 133 healthy mature women, 124 pregnant women, and 37 postmenopausal women. These levels were highest in the premenarchal teenagers, and became successively lower in the postmenarchal teenagers, the mature women, and the pregnant women, so that the mean level of the pregnant women was less than half that of the teenagers. The CK levels then rose again after the menopause. If the distribution of CK levels in adult non-pregnant women had been taken as controls for teenagers who were possible carriers for Duchenne muscular dystrophy, then one third of those teenagers classified as carriers would have been so classified incorrectly. [ABSTRACT FROM PUBLISHER]

Pedigrees of Duchenne muscular dystrophy were sent to 32 geneticists in the United Kingdom, asking for their calculations for genetic risks for female relatives. Eighteen participated, of whom only 7 gave correct answers for all pedigrees. The method most used for calculations (the 'Bayesian' method) was most liable to errors in new situations. An alternative, simpler method is presented. [ABSTRACT FROM PUBLISHER]

A family study of 32 patients with torsion dystonia has shown at least two forms of generalized dystonia with onset in childhood. These two forms, an autosomal dominant and an autosomal recessive, are clinically indistinguishable. There were at least three families and probably about six to eight patients with the autosomal recessive variety. The remaining nine to 11 patients with generalized childhood dystonia are thought, because of a probable paternal age effect, to be examples of new dominant mutations. Since fitness with childhood onset is 1/20 of normal, most childhood dominant cases appear sporadically. Most of the other 15 patients (12 with onset in adult life) appear to have a non-genetic torsion dystonia, although an example of a benign adult-onset dominant form associated with a tremor has been observed. It is concluded that there are at least two forms of genetic torsion dystonia, an autosomal recessive form with onset in childhood, which, on evidence from America, is particularly common in Ashkenazi Jews, and one or more dominant forms, with onset in childhood or adult life. The majority of adult-onset isolated cases of idiopathic torsion dystonia seem to be due to exogenous but unidentified causes. [ABSTRACT FROM PUBLISHER]

From the present study, and from reports in the literature, two forms of childhood myasthenia emerge. There is an early-onset form (with onset of symptoms under 2 years of age) where the illness is milder but more persistent, and where there is frequent occurrence of myasthenia in sibs. Such cases are likely to be inherited as an autosomal recessive, although it is possible that they represent the extreme edge of a multifactorial distribution of combined genetic and environmental aetiology. The second group (with onset of symptoms between the age of 2 and 20 years) clinically resembles adult myasthenia, which is associated with autoimmunity and an increased incidence of thyroid dysfunction. Some genetic contribution occurs in this form but it is less marked than with the early-onset cases and there is no recognizable pattern of inheritance. As secondary cases are even less common among the families of adult myasthenics, it is likely that individuals with most genetic predisposition to myasthenia tend to develop symptoms early, and that non-genetic factors are relatively more important for the development of myasthenia in adults. [ABSTRACT FROM AUTHOR]

A study has been performed on 124 first degree relatives of 38 index patients with dystrophia myotonica in order to assess means of detecting heterozygotes before neurological complaints. Some or all of the following tests have been performed on the relatives: clinical examination, electromyography, slit-lamp examination, radiography of the skull, electrocardiography, serum insulin, and serum immunoglobulin levels. There is evidence that abnormalities in symptomless heterozygotes may be detected by slit-lamp examination, electromyography, and immunoglobulin concentration, and this is probably the order of usefulness of the test in early recognition of the disease. In this study 13 previously undetected heterozygotes have been identified: six as a result of neurological examination, four by both electromyography and slit-lamp examination, and three by slit-lamp examination alone. Abnormalities detected by these tests appear to be independently manifest, so that they will probably be more useful in combination than singly. The family data give a maximum estimate for incidence of mutations among index cases of one quarter, lower than previously suggested. The estimation of immunoglobulins in 45 patients showed significant deficiency, as compared with controls, not only of IgG but also of IgM, and there was an insignificant trend for IgA to be low too. This suggests that the abnormally rapid catabolism of immunoglobulin, previously reported, is not specific for IgG. [ABSTRACT FROM AUTHOR]