Showing papers in "Journal of Medical Genetics in 1981"

Localisation of male determining factors in man: a thorough review of structural anomalies of the Y chromosome.

Abstract: It is widely accepted that male determination in man depends on the presence of a factor or factors on the Y chromosome. These factors may be localised within the Y chromosome through the study of structural anomalies of the Y. A thorough review of seven different structural anomalies of the Y is presented: dicentric Y chromosomes, Y isochromosomes, ring Y chromosomes, Y; autosome, Y;X, and Y;Y translocations, and Y deletions. The evidence from these studies indicates that a gene or genes on the short arm or the Y near the centromere play a crucial role in the development of the testes. A few studies indicate that one or more factors on the long arm of the Y may also influence testicular development. If such a factor is present on the long arm, then it too must be very near the centromere. The theory that separate genes independently control the initial development and maturation of the tests (on the long and short arms of the Y, respectively) may be premature. Recently proposed arguments in its favour are examined. Some evidence also indicates the presence of a fertility factor on the non-fluorescent segment of the long arm. Relevant information on the H-Y antigen is discussed.

Translocation (X;6) in a female with Duchenne muscular dystrophy: implications for the localisation of the DMD locus.

Abstract: A female with Duchenne muscular dystrophy who was a carrier of a balanced translocation t(X;6)(p21;q21) is reported. Four other previously described (X;A) translocations associated with DMD share with the present case a breakpoint at Xp21. The extremely low probability of five independent (X;A) translocations having a breakpoint at Xp21 points to a non-rand association of this site with the DMD phenotype. A DMD locus at Xp21 could be damaged by the translocation, giving rise to Duchenne muscular dystrophy. Alternatively, a pre-existing DMD gene could weaken the chromosome, favouring breaks at Xp21.

5-Fluoro-2'-deoxyuridine induction of the fragile site on Xq28 associated with X linked mental retardation.

Abstract: 5-Fluoro-2'-deoxyuridine (FUdR) was found to be highly effective in inducing the heritable fragile site on Xq28 associated with mental retardation. Lymphocytes from two affected males manifested the fragile site in 30 to 40% of the mitoses when grown in the presence of FUdR. This observation suggests that depletion of the dTMP pool via thymidylate synthetase inhibition is responsible for the expression of the heritable fragile site on Xq28.

Genes for super-intelligence?

Abstract: The results of a postal questionnaire distributed to British members of Mensa failed to confirm an association of superior intelligence with torsion dystonia, retinoblastoma, or phenylketonuria, but were consistent with real associations between high IQ and infantile autism, gout, and myopia. Further confirmation of these findings in other populations might well indicate that genes producing these disorders have more or less direct effects on cerebral development and function.

Effectiveness of one tube osmotic fragility screening in detecting beta-thalassaemia trait.

Abstract: The effectiveness of the one tube method of osmotic fragility with three buffered solutions (0.32% saline, 0.36% saline, and tyrode) as a screening test for beta-thalassaemia trait was evaluated in several groups of subjects from Greece, Yugoslavia, and Thailand. The results clearly demonstrated that 0.36% saline is the most sensitive and effective solution since it could detect 96 to 100% of heterozygotes with beta-thalassaemia, compared to about 80% with both 0.32% saline and tyrode. However, 0.36% saline gave false positive results in normal subjects and was also positive in haematological disorders which influence osmotic fragility. The screening test with 0.36% saline was applied more precisely in 1371 subjects. The test was false positive in 41 (9.1%) of 455 normal subjects while of 438 confirmed heterozygotes with beta-thalassaemia it was positive in 431 (98%) and negative in only seven (2%). The test was also found to be positive in 80% of patients with iron deficiency anaemia and alpha-thalassaemia trait, in 68% of patients with Hb E trait, in 40% of patients with Hb S trait, and in 78% of heterozygotes with rare haemoglobin variants. The increased sensitivity and effectiveness of 0.36% saline in detecting beta-thalassaemia trait and other disorders influencing osmotic fragility as compared to 0.32% saline and tyrode solutions was also confirmed in a study of 384 unselected schoolchildren.

Asplenia and polysplenia syndromes with abnormalities of lateralisation in a sibship.

Abstract: In the family presented here the first child had asplenia syndrome with cor biloculare' transposition of the great vessels, pulmonary stenosis, and anomalous pulmonary venous drainage. Another sib had situs inversus with polysplenia syndrome, including very similar cardiovascular defects and biliary atresia. The possibility that these two syndromes, namely asplenia and polysplenia, are different manifestations of a similar defect in the normal asymmetrical development of internal organs is discussed.

Multiple pterygium syndrome.

Abstract: The multiple pterygium syndrome is a rare autosomal recessive condition characterised by arthrogryposis multiplex congenita, pterygia of the neck, fingers, and antecubital, popliteal, and intercrural areas, growth retardation, and facial, vertebral, and genital anomalies. We present two unrelated patients of 17 and 6 years of age, respectively, affected with this condition. We describe the natural history of their disorder since birth and review the spectrum of phenotypic variation of the multiple pterygium syndrome in 25 published cases.

Tetraploidy in a liveborn infant with spina bifida and other anomalies.

Abstract: Although tetraploidy of human chromosomes (92,XXYY) has been described frequently in abortuses, only one example in a liveborn infant has previously been described. A second malformed infant with a complete tetraploid chromosome complement, who lived for 15 days, is reported. In addition to many of the malformations described in the first case, this infant also had a sacral myelomeningocele and skeletal anomalies. The probable origin of the tetraploidy was a failure of cytoplasmic cleavage at the first mitotic division of the fertilised ovum.

Down syndrome associated with father's age in Norway.

Abstract: Records of births in Norway in 1967 to 1978 were examined for evidence of an increased risk of Down syndrome associated with older paternal age. From among some 685 000 total births with known maternal and paternal age, 693 cases of Down syndrome were reported to the Medical Birth Registry of Norway. The effect of paternal age was assessed by classifying fathers as young and old on the basis of several definitions. The effect of maternal age was removed by stratifying the data on single years of mothers' age. When fathers were considered young if they were less than or equal to 49 and old if they were less than or equal to 50, the analysis yielded a statistic for the test of a one-sided hypothesis which was significant at the 0.05 level. There appears to be an increase risk (perhaps 20 to 30%) of Down syndrome associated with older fathers, independent of maternal age effect. If this increase does in fact exist, it is much smaller than the increases in risk associated with advancing maternal age, and because older men contribute a relatively small proportion of total births their contribution to the communal burden of Down syndrome is quite small. However, the finding is of aetiological interest and is the first indication of a significant paternal age effect where control for maternal age has been stringent.

Poland-Möbius syndrome.

Abstract: A patient with stigmata of both the Mobius syndrome and the Poland syndrome is presented. This is now the twelfth well-documented patient with a combination of the two syndromes. The association of the Poland syndrome and the Mobius syndrome occurs with sufficient frequency that the combination probably represents a formal genesis malformation syndrome of unknown aetiology that should be designated the Poland-Mobius syndrome.

The 'fragile' X chromosome in the Martin-Bell-Renpenning syndrome and in males with other forms of familial mental retardation.

Abstract: A clinical and cytogenetic study has been made of subjects from families who have possible X linked mental retardation. The families were distinguished as those with a clinical diagnosis of Renpenning syndrome and those with other behavioural or physical abnormalities obviating such a diagnosis. All subjects with REnpenning syndrome carried a fragile Xq27-28 chromosome in more than 4% of their blood lymphocytes. In addition, two other families who did not have Renpenning syndrome but had similar clinical features also carried the fragile site Xq27-28. A female age effect was observed and one possible carrier of Renpenning syndrome exhibited the fragile X in 10% of her lymphocytes but was also mentally retarded. Subjects within the same family did not always exhibit the fragile site on a comparable proportion of their cells.

Genetic aspects of autosomal dominant late onset cerebellar ataxia.

Abstract: The genetic features of eight families with autosomal dominant late onset cerebellar ataxia with randomly distributed associated clinical features are described. The ratio of affected to unaffected offspring of affected subjects was not significantly different from 1:1. The mutant gene was fully penetrant when cases who died before the period of risk of developing the disease were excluded. The proportion of new mutants with this disorder appears to be low. Biological fitness was not impaired. Affected females tended to have large families than affected males. The ages of onset of females and males were not significantly different, but the offspring of affected males had earlier ages of onset and death than those of affected females. A cumulative age of onset curve is presented which should aid genetic counselling of subjects at risk and their children.

Human acetylator polymorphism: estimate of allele frequency in Libya and details of global distribution.

Abstract: Acetylator phenotyping by means of a sulphadimidine tests revealed 65% of Libyan Arabs to be slow acetylators. Hence the frequency of the allele controlling slow acetylation (As) is estimated as q = 0.81 +/- 0.05. This estimate is similar to those previously recorded in European and adjacent Middle Eastern populations.

Objective knowledge about Huntington's disease and attitudes towards predictive tests of persons at risk.

Abstract: The task of genetic counselling of people at risk for Huntington's disease might be facilitated by increased knowledge of relevant population characteristics. The aim of the present study was to clarify select socioeconomic characteristics, knowledge concerning the disease, and attitudes towards predictive tests of people at 50% risk of inheriting Huntington's disease in the state of Victoria. A random sample of subjects was drawn from the Huntington's disease register and 50 questionnaires were analysed. Respondents completed three questionnaires which covered their socioeconomic characteristics, the extent and accuracy of their knowledge about the genetic, progress, and treatment of Huntington's disease, and their attitude and acceptance of predictive tests as well as their intentions about future reproduction. A very positive attitude was found to be held by the respondents towards a predictive test if it was safe, reliable, and non-invasive. Resultant problems which would arise, should a reliable test be found, are discussed. The respondent's knowledge concerning the disease was found to be adequate generally.

'Pseudo-dominant' inheritance in Friedreich's ataxia.

Abstract: A family is described in which Friedreich's ataxia occurred in two generations. It is proposed that this resulted from a homozygote-heterozygote mating. The heterozygote frequency for the Friedreich's ataxia gene is in the order of 1 in 110, so the likelihood of the disease developing in an individual child of a patient is 1 in 220. This risk is probably higher than that often assumed when counselling patients with this disorder.

Ring chromosome 14: a distinct clinical entity.

Abstract: An infant girl with ring chromosome 14 is presented The findings in this patient and in six previously reported cases of a ring 14 suggest that a characteristic clinical syndrome is associated with this chromosome aberration The major features of the ring chromosome 14 syndrome include mental retardation, a disorder of skin pigmentation, seizures, and dysmorphic features, including flat occiput, epicanthal folds, downward slanting eyes, flat nasal bridge, upturned nostrils, short neck, and large low set ears

Risks to the offspring of patients with some common congenital heart defects.

Abstract: The families of 424 adult index patients with ventricular septal defect, right ventricular outflow tract obstruction, or combinations of these two abnormalities, were visited and interviewed, and whenever possible the children of index patients were examined clinically. Congenital heart defects were present in 9 of 308 children, 8 of 899 sibs, 4 of 840 parents, and 4 of 731 nephews and nieces of the index patients. The last three figures are likely to be underestimates owing to the design of the study. Comparison of pairs of affected relatives suggests that the group of lesions studied may have genetic determinants in common.

Recurrence risks for neural tube defects in a genetic counseling clinic population.

Abstract: The recurrence of neural tube defects (NTD) in the sib following the index case of all patients who consulted the South-East Thames Regional Health Authority Genetics Centre in the period 1972 to mid-1979 was calculated. A total of 1037 consecutive patients was studied, of whom 958 (93%) were traced. The overall recurrence was 3.44% (1 in 29). However, if the index case was the first affected child in the family, the recurrence in the next sib was 3.15% (1 in 32), and if it was the second affected child, the recurrence was 11.76% (1 in 9). These figures give an indication of the actual recurrence among the 'selected' population who consult a genetic advice centre, and are somewhat, but not significantly, different from figures for the general NTD population, which have been derived from studies of whole families.

Inheritance of a ring 14 chromosome.

Abstract: A family is described in which the mother, her two live offspring, and a therapeutically aborted fetus each had a ring 14 chromosomes. The two children were mentally retarded and the mother's intelligence was at the lower end of the normal range. In addition, the mother had two spontaneous abortions, one of which was shown to be chromosomally normal.

Hereditary multiple exostoses: report of a kindred.

Abstract: In a large family with 37 members with multiple exostoses, only one person has developed sarcomatous degeneration of a lesion. Our review of published reports revealed great variation in the incidence of malignancy in multiple exostoses (10 to 25%). Most studies had sampling errors leading to the apparent overstatement of risk. In large pedigrees with essentially complete ascertainment of affected subjects, the risk of malignancy is nearer 3% or less. This lower risk for malignancy may be more appropriate in counselling affected subjects.

18p— syndrome with a single central maxillary incisor

Abstract: A child with a single central maxillary incisor and a deletion of the short arm of chromosome 18 (18p—) is presented. He is the first patient in whom this association has been found.

A case of trisomy of chromosome 15

Abstract: We describe a case of trisomy of chromosome 15 in an infant who presented at birth with numerous abnormalities. As far as we are aware this chromosomal abnormality has not been described before. On the basis of this one case there appear to be no features which are specific to this chromosomal abnormality.

A family study of hydrocephalus resulting from aqueduct stenosis.

Abstract: Stenosis of the aqueduct of Sylvius accounts for about one third of cases of congenital hydrocephalus. At least 32 families have been reported in which the aqueduct stenosis is inherited in an X linked fashion. In half of these families, flexed adducted thumbs were noted in some affected family members. Occasionally other male members were mentally retarded, suggesting limited expression of the gene. The problem of giving genetic advice to an isolated, clinically unremarkable, case of aqueduct stenosis remains, so a family study was undertaken based on 24 such cases seen at The Hospital for Sick Children over a 19-year period. There were 15 male and nine female index patients. The diagnosis was confirmed in all cases by air encephalogram. One boy had a radial club hand and another developed clasped thumbs secondary to spasticity. No cases had hyaloidoretinal dysplasia. The 15 boys had 18 brothers and 19 sisters, of whom one sister was similarly affected. The nine girls had 12 sibs, none of whom was affected. This study, combined with a similar study in the USA, suggests that the empirical risk of recurrence of a sporadic case of aqueduct stenosis is about 4.5%.

Syndromes of microcephaly, microphthalmia, cataracts, and joint contractures

Abstract: Three infants are described, one with the Neu-Laxova syndrome and two with the cerebro-oculo-facio-skeletal (COFS) syndrome. The relationship between these two syndromes is discussed in the light of the present cases and others in published reports.

The aetiology of the cat eye syndrome reconsidered.

Abstract: The cat eye syndrome (CES), usually ascribed to the presence of a deleted supernumerary 22 chromosome, is characterised by a typical clinical picture including anal atresia, ocular coloboma, preauricular tags or sinuses, congenital heart defects, urinary tracts anomalies, and mental and physical retardation An analysis of published reports revealed that of the 57 reported cases, only 21 showed the complete form, and 11 had a normal karyotype Several observations question the existence of a trisomy 22:(1) the absence of any report in living subjects of trisomy 22 arising from an inherited Robertsonian translocation; (2) the recurrent abortions in carriers of Robertsonian translocations involving chromosome 22; and (3) the existence of a syndrome, showing the same clinical features as trisomy 22, which is irrefutably dependent on a trisomy of the distal region of the 11 long arm On the basis of a comparison of the clinical features in full trisomy 13, partial 13 trisomies, 13 rings, 13 deletions, and CES the small marker present in this syndrome is considered to be a chromosome 13 with an interstitial deletion An attempt to map this chromosome has been made

Hydrocephalus, agyria, pseudoencephalocele, retinal dysplasia, and anterior chamber anomalies.

Abstract: An infant presenting with hydrocephalus, pseudoencephalocele, agyria, and ocular defects, consisting of anterior chamber anomalies and retinal dysplasia, is reported. This is thought to be a further case of an autosomal recessive syndrome of which six cases have been previously described.

Trisomy 14 mosaicism in a translocation 14q15q carrier: probable dissociation and isochromosome formation.

Abstract: A case of trisomy 14q mosaicism is described and compared with three other similar reported cases. The clinical picture is characterised by severe developmental retardation, failure to thrive, and somatic abnormalities including skeletal asymmetry, high arched or cleft palate, and low set dysplastic ears. The present chromosome imbalance probably resulted from dissociation of a balanced 14q15q translocation with subsequent formation of a 14q isochromosome.

Partial trisomy 12q: report of a case and review.

Abstract: A malformed male infant with pure partial trisomy 12q (q24.1 leads to qter), resulting from an unbalanced segregation of a paternal balanced translocation t(2;12)(q37;q24.1), is described. The cytogenetic and clinical abnormalities of the proband are compared with those of four previously reported cases of partial trisomy 12q, two of which also appear to have pure trisomy of segment 12q24.1 leads to 12 qter.

Partial trisomy 12q.

Abstract: A partial trisomy 12q243 leads to qter resulting from a maternal balanced translocation, 46,XX,t(9;12)(p243;q243) was detected in a male newborn with multiple congenital abnormalities. The maternal grandmother was also a carrier of the 9;12 translocation. Our patient exhibited a number of clinica features similar to two others reported, who were also trisomic for the distal part of 12q. Aberrations of chromosome 12 are very rare. There have been only two reports of partial trisomy 12q, both the result of a familial translocation. We describe a third unbalanced case.

Complete trisomy 9 in two liveborn infants.

Abstract: Two unrelated newborn infants with multiple malformations were found to have complete trisomy 9 in all cells examined. In both, the phenotype was similar, consisting of characteristic facial appearance (microphthalmia, bulbous nose, micrognathia, cleft palate, low set ears), skeletal abnormalities (dislocated joints, flexion contractures of the fingers), cardiovascular malformations (persistent left superior vena cava, ventricular septal defect), hypoplastic genitalia, renal anomalies, and central nervous system malformations. Both died during the first few hours of life. Comparison of these two infants with the previously reported cases reveals a consistent pattern of malformations and very short survival associated with trisomy 9. These cases illustrate the importance of doing chromosome studies on infants with congenital malformations dying in the newborn period and the usefulness of such studies in counselling parents regarding the risk of recurrence.