Interstitial deletion of distal 13q associated with Hirschsprung's disease.

Three cases of interstitial deletion of chromosome 13 involving the common segment 13q22.1----q32.1 are reported. In addition to the recognised clinical features of this deletion, two had Hirschsprung's disease.

Hydrocephalus, tall stature, joint laxity, and kyphoscoliosis: a new inherited disorder of connective tissue?

We describe two sisters with hydrocephalus, tall stature, joint laxity, and thoracolumbar kyphosis.

Aetiology of mild mental retardation.

A clinical and family study was carried out in 169 children attending schools for the mildly mentally retarded in Southampton to assess the prevalence of recognised medical risk factors; 71 children (42%) had such risk factors. These were prenatal in 22, perinatal in 41, and postnatal in eight. Risk factors of possible, but less certain, significance were found in a further 63 children (37%). In 86 families (51%) there was a history of serious educational problems in both parents. The prevalence of both types of risk factor was higher in the children whose parents had no educational problems. There were, however, 25 children (15%) whose parents had no history of educational problems and in whom medical risk factors were either absent or minimal.

The socio-familial background and prevalence of medical aetiological factors in children attending ESN/M schools.

A study of 169 midly mentally retarded children included consideration of social class, medical risk factors, sibship position, family size and parental education. Ninety-four (56%) children were from social class IV or V. Medical risk factors were identified in 71 (42%) children overall: the prevalence fell from 55% in social class II to 30% in social class V. Prenatal factors were identified in 22 children of whom 14 were third or later born in their sibship: this may reflect increased maternal age at birth. Perinatal events had been reported in 41 children, 20 of whom were in social class III; there was no clear relationship to sibship position. Seven of eight postnatal events had occurred in children in social class II or III. Children in social class IV or V did not appear to be at increased risk of retardation from environmental medical events. Firstborn children were over-represented in the survey, with a minor shift towards fourth-or later-born children. Average family size was 3.25 children (general population 2.0 children). The prevalence of medical risk factors was lowest (18%) in children from large sibships in social class V. Both parents of 86 children had had educational problems: this included 13 children in social class III. Thirty-eight (33%) of these children had medical risk factors, compared with 43/83 (51%) in children where at least one patient had achieved average education. Thirty children had no medical risk factor, nor any history of parental learning difficulty.

Chromosome abnormalities in pupils attending ESN/M schools.

One hundred and sixty six children attending educationally subnormal/mild (ESN/M) schools were karyotyped as part of a project investigating the aetiology of mild mental retardation. Nine had significant chromosome abnormalities. Five of six children identified during the survey had no dysmorphic features--47,XXY (two), 48,XXYY, 46,XX 15q-, and 46,XX,t(X;19). One dysmorphic boy had a balanced translocation--46,XY,t(3;15). Three were already known--47,XX+21 (two) and 46,XY, 14q+. We suggest that routine karyotyping of children with mild mental retardation be considered.

Chromosome abnormality in couples with histories of multiple abortions. The outcome of pregnancies subsequent to ascertainment and a study of familial translocation carriers.

A series of couples with histories of recurrent abortions and in whom one partner had been shown to have a major chromosomal anomaly were investigated with respect to the karyotypes of conceptions subsequent to ascertainment. The reproductive histories of translocation carriers amongst relatives were also studied. Results were compatible with previous reports of the behaviour of translocation chromosomes at meiosis with an additional previously undescribed outcome as a result of a maternal 13/14 Robertsonian translocation.

Isodicentric X chromosome in a moderately tall patient with gonadal dysgenesis: lack of effect of functional centromere on inactivation pattern.

An isodicentric X chromosome (46, X idic (X)(pter leads to qter::qter leads to pter)) with a single functioning centromere was found in all lymphocytes and fibroblasts examined from a female patient 171.5 cm in height presenting with primary amenorrhoea. Replication of the abnormal chromosome was consistently late. In some cells the pattern was asymmetrical but the asymmetry did not appear to relate to the position of the active centromere.

Cytogenetic and histological studies of testicular biopsies from subfertile men with chromosome anomaly.

Testicular biopsies from eight men with abnormal karyotypes have been examined for histological and cytogenetic evidence of disturbances of meiosis. Quantitative analysis of this material showed one, with a 13;14 Robertsonian translocation, to have apparently normal spermatogenesis. Three patients, one with a 47,XYY and two with 45,XY, inv 9 karyotypes, had an overall depression of spermatogenesis. Four others, all with major chromosomal abnormalities, had apparently normal spermatogenesis until the primary spermatocyte stage. Two of these had sex autosomal translocations. One, 45,Y,t(X;21), had a complete block at MI, the other, 46,X,t(Y;16), had a partial block at spermatid formation. One man with a reciprocal 2;10 translocation showed delay at all stages beyond spermatocyte formation and one man with an inversion of chromosome 3 showed impaired spermatid maturation.

Comparative studies of spermatogenesis in fertile and subfertile men.

Testicular biopsy specimens from 16 fertile and 10 subfertile men with normal male karyotype were studied quantitatively to provide histological and cytogenetic data for a basis of reference in assessing abnormalities of spermatogenesis. Histological studies included estimation of the proportion and activity of germinal epithelium and an assessment of tubular morphology. In cytogenetic preparations, counts were made of cells at different stages of meiosis. Studies of cells at diakinesis included chiasma counts and percentage of cells with dissociated sex chromosomes. One fertile and six subfertile men showed decreased germinal activity; the six subfertile men also had decreased MII/MI ratios. Other findings were similar in the two groups.

HLA antigens in a Scottish psoriatic population.

Sixty-one patients in the Dundee area suffering from psoriasis were typed for HLA-A and HLA-B antigens. On the basis of the typing results, the patients were divided into three groups, and studied with respect to sex, age of onset and familial incidence of the disease. The frequency of HLA-A1 appeared to be increased and HLA-B7 decreased but HLA-B13 and HLA-B17 were highly significantly increased (P less than 10(-6) and P less than 10(-10) respectively) in the psoriatic group compared to 204 controls. Of particular interest was a highly significant association of HLA-A1 with HLA-B17 in psoriatic patients. Family studies showed HLA-B17 to be a useful genetic marker for psoriasis in the families of B17 positive patients. Considerations of age of onset, familial incidence and typing data suggest that there is heterogeneity of genetic susceptibility to psoriasis and that one probable mechanism is the dominant inheritance of a "disease allele" in linkage disequilibrium with the allele coding for HLA-B17.

A cytogenetic survey of men being investigated for subfertility.

A study of 336 men attending a subfertility clinic but otherwise unselected, and a further 12 men studied as a part of the investigation of the female partner, revealed 10 with major chromosome anomaly and 3 with unambiguous chromosomal variants. In addition to those with sex chromosome aneuploidy, an extra, small marker chromosome and D/D Robertsonian translocations, anomalies which have been reported in other studies, there were 7 men with rearrangements, including a paracentric inversion of chromosome 7 and an X/21 reciprocal translocation. These would have been difficult or impossible to identify without good banded preparations, suggesting that such rearrangement may be more frequent in association with subfertility than was appreciated.