Showing papers in "Journal of Medical Genetics in 1972"

The dominant and recessive forms of cutis laxa.

Abstract: Cutis laxa is a very rare, genetically determined disorder of elastin, characterized clinically by a tendency of the skin to hang in loose folds, with the production of a typical grotesque facies and the appearance of premature ageing. These changes may be present at birth or may develop during infancy. Systemic ramifications may be widespread and, in particular, the pulmonary and cardiovascular systems may be involved. Although less than 30 genuine cases have been reported there have been several instances of serious disability or death from cardiorespiratory complications. On the other hand, a significant proportion of the affected patients have lived comparatively normal existences. In the course of a recent survey, in which complete ascertainment of all affected individuals in England and Wales was attempted, it became apparent that there were two forms of the condition,

Four patients with trisomy 8 identified by the fluorescence and Giemsa banding techniques.

Abstract: The C group chromosomes in man cannot be distinguished solely on morphological grounds, thus, the nature of an extra C chromosome remains unknown unless it is an X chromosome, which can be identified by its late DNA-replication pattern. Extra autosomes belonging to the C group have been observed with or without mosaicism in a wide variety of blood disorders (cf, de la Chapelle et al, 1970; Hellstrom et al, 1971), in spontaneous abortions (Boue and Boue, 1969), in malformed and/or mentally retarded subjects (Pfeiffer, Schellong, and Kosenow, 1962; El-Alfi, Powell, and Biesele, 1963; Stalder, Buhler, and Weber, 1963; Stolte, Evers, and Blankenborg, 1964; Wolf and Reinwein, 1965; Jalbert et al, 1966; Kerr and Rashad, 1966; Schutt, 1966; Juberg, Gilbert, and Salisbury, 1970), in one female with primary amenorrhoea (Jacobs et al, 1961), and in one apparently healthy female who gave birth to malformed children (Smith, 1964). This great variation in the clinical picture speaks in favour of different C autosomes having been involved, an hypothesis which has-so far-been impossible to test. The fluorescence and Giemsa banding techniques offer a new possibility to study this problem, and in the present work we describe 4 patients with an extra C chromosome all identified

Camurati-Engelmann disease. Genetics and clinical manifestations with a review of the literature.

Abstract: This syndrome, which usually carries the names of Camurati and Engelmann, was first described by Cockayne in 1920. Its hereditary nature was suggested by Camurati (1922) who reported a father and son both with painful lower extremities which showed cortical thickening and sclerosis of the diaphyses on x-ray examination. The single case report of Engelmann in 1929 documented muscular wasting and marked bone involvement. Neuhauser et al (1948) subsequently named this rare condition 'progressive diaphyseal dysplasia' emphasizing the progression of the hyperostosis along the shafts of the bones. Subsequently, both sporadic and familial cases have been described. This report is the result of the authors' unusual opportunity to study extensively a large, cooperative family with 8 affected individuals in 3 generations, representing the largest affected kindred to date. Our observations in this family, together with those from the literature, demonstrate the considerable variability of this autosomal dominant inherited disorder. Clinical and genetic considerations are stressed here, and the radiological manifestations are discussed in greater detail elsewhere (Graham and Sparkes, 1972).

Popliteal pterygium syndrome. Evidence for a severe autosomal recessive form.

Abstract: The term 'popliteal pterygium syndrome' has been used to distinguish a constellation of congenital anomalies characterized by cleft palate, with or without cleft lip, lip pits, popliteal and other webs, toenail dysplasia, syndactyly, aplasia of the labia majora, and other anomalies. The syndrome may be associated with mental retardation. About 48 cases of this inherited syndrome have been reported in the literaturet since Trelat's first description in 1869. The genetic pattern by which the popliteal pterygium syndrome is transmitted has however not yet been firmly established (Smith, 1970). An additional family with this syndrome is reported.

Familial chronic muco-cutaneous candidiasis.

Abstract: Chronic oral candidiasis has been described in association with abnormalities of the endocrine system on many occasions, both in case reports (Sutphin, Albright, and McCune, 1943), and more general reviews (Kunin et al, 1963). Chronic candidiasis has also been recorded in the familial thymic aplasia described by Nezelof (Nezelof et al, 1964), Swiss-type agammaglobulinaemia (Hitzig, 1968) and DiGeorge's syndrome (DiGeorge, 1965). More recently deficiency of the migration inhibitory factor (MIF), where cell mediated immunity appears to be partially defective, has been shown to be a feature of some patients with chronic candidiasis (Valdimarsson et al, 1970). It has also been associated with defective granulocyte function, as in chronic granulomatous disease (Quie et al, 1967) and myeloperoxidase deficiency (Lehrer and Cline, 1969). During the last 3 years a group of patients has been investigated (Wells, 1970) who have chronic oral candidiasis with no other significant clinical abnormality. In some of the kindreds, sibs were found to have the disorder, and there was often a family history of consanguinity. We have suggested that this new group, hitherto undescribed and which we have called familial chronic mucocutaneous candidiasis (FCMC), has a genetically determined abnormality, inherited as an autosomal recessive trait which results in susceptibility to candida infection. It is possible that an inherited biochemical or immunological abnormality results in this picture.

A ring-20 chromosome.

Abstract: to be devoid of any genes or factors necessary for normal male development, this raises questions as to why it exists in its present form, and whether it may have some other functions. The existence of the fluorescing portion of the Y long arm may be explained as the result of evolutionary change involving the accumulation of non-functional genes on sheltered chromosomes, which Nei (1970) has demonstrated can occur in a reasonable period of evolutionary time. This process may explain the observed polymorphism in Y length, for unlike the X chromosome, in which deletions or duplications could present problems during meiosis, the Y chromosome has no similar restrictions. Furthermore, since survival is possible without the Y but not without an X chromosome, and since both theX and Y are believed to have evolved from a homologous pair of autosomal chromosomes, there must have been preferential inactivation of the genes of the Y chromosome. This inactivation would promote differentiation between the sex chromosomes and reduce the possibility of crossing-over. Lack of differentiation between the gonosomes could put a species at a selective disadvantage by making for a high incidence of intersex. That such inactivation occurred is suggested by the fact that there is virtually no recombination between the X and Y in organisms with well-differentiated sex chromosomes (Nei, 1970). Despite the lack of structural genes, it is possible that the fluorescing Y long arm does have a function in orienting this chromosome in the sex bivalent during meiosis, when, as has been shown by Pearson and Bobrow (1970), the short arm of the Y enters into a terminal association with the X chromosome. The fact that fertility was not impaired in the present family may indicate that the Y aberration is indeed an isochromosome of the short arm, in which case it would not matter which end associated with the X. On the other hand, diminished fertility was noted by Muldal and Ockey (1962) in a family in which nearly one half of the Y long arm was deleted; and dicentric Ys are associated with infertility, with the X and Y appearing as univalents in the majority of cells at diakinesis (McIlree et al, 1966).

The polymorphic acetylation of sulphapyridine in man.

Abstract: Since 1941 salicyl-azo-sulphapyridine (sulphasalazaline) has been used in the treatment of ulcerative colitis (Svartz, 1942). The drug undergoes extensive cleavage of the azo linkage in vivo (Svartz, Kallner, and Helander, 1945; Bottiger and Mollerberg, 1959; Schroder and Campbell, 1971) and the sulphapyridine thus formed is subject to N4-acetylation and simultaneous ring hydroxylation. The hydroxylated metabolite is recovered in the urine entirely as its 0-glucuronide. The absence of free hydroxylated sulphapyridine in urine indicates that the hydroxylation is the rate-determining step in the formation of the glucuronide (Schr6der and Campbell, 1971). The disposition of sulphapyridine in man is shown in Fig. 1.

The use of new staining techniques for human chromosome identification.

Abstract: An accepted feature of technological development and its associated accumulation of data is that progress occurs in an irregular fashion with 'break throughs' being interspersed by periods of relative inactivity. In the halcyon years of 1955 to 1961, human cytogenetics experienced a revolution which brought the field within the scope of most genetic laboratories. The resulting increase in the volume of cytogenetical data being published has seen few parallels in the history of science. A review of the period (Hamerton, 1962) amply demonstrates the accurate level of information gathered over this era, and one concludes that, with the exception of autoradiographic information at that time, the technique not yet having been applied to human cytogenetics, very little new information was collected over the next 8 years. The majority of contributions merely emphasized biological situations known to exist and described in part previously. Over this period, the limitations in identifying human chromosomes on morphological criteria remained a major deficiency of the work and the IIIrd Chromosome Standardization Conference (Chicago Conference, 1966) summarized and defined those chromosomes which could be further specified by a combination of their morphological and autoradiographic patterns. Only those who have had cause to use autoradiography for chromosome identification will appreciate the strictures imposed by time, resolution, and sample size by this technique. This was the less than satisfactory state of the art in late 1968 when a group from the Karolinska Institute, Stockholm, led by T. Caspersson, published what was to be the first ofan astonishing series of papers. In the first paper (Caspersson et al,

A twin study of the genetic influences on the electroencephalogram.

Abstract: Many attempts have been made to relate individual differences in the background electroencephalogram (EEG) to various psychiatric conditions (Glaser, 1963; Hill, 1963; Wilson, 1965) and equivalent investigations have recently been carried out with the averaged evoked response waveform (Shagass and Schwartz, 1961, 1962, 1963, and 1965; Jones et al, 1965; Callaway, Jones, and Donchin, 1970) and the alpha attenuation response (Blum, 1957; Wells and Wolf, 1960; Davidoff and McDonald, 1964; Milstein, Stevens, and Sachdev, 1969). The last two measures represent changes induced in the EEG by stimulation. The main features of the spontaneous EEG show marked between subject variability but a tendency towards consistency and long-term stability within the same individual (Hill, 1963). Similar characteristics have been described for the averaged evoked response waveform (Dustman and Beck, 1963 and 1965) and the alpha attenuation response (Fenton and Scotton, 1967; Milstein et al, 1969). While there is strong presumptive evidence that the interindividual differences in the background EEG are influenced by genetic factors, the exact role of heredity remains unknown (Clarke and Harding, 1969). There have been no previous systematic investigations of the genetic aspects of the alpha attenuation response, but the contribution of heredity to the individual variation in the averaged evoked response is claimed to be substantial (Dustman and Beck, 1965). These findings however remain unconfirmed. In the present study, standardized EEG recordings were obtained from 64 well matched, identical and fraternal twins and measures made of the spontaneous EEG and the alpha attenuation and the averaged evoked responses. By this means, the genetic component of variation of the spontaneous

Pyloric atresia. A hereditary congenital anomaly with autosomal recessive transmission.

Abstract: Pyloric atresia is a rare congenital anomaly; to date, only 29 newborns with this defect have been reported. Though familial occurrence of this anomaly has been reported twice (Benson and Coury, 1951; Thompson et al, 1968; Bronsther, Nadeau, and Abrams, 1971), no previous comments have been made concerning a possible genetic aetiology. The purpose of this paper is to report 5 additional familial cases* from two unrelated Israeli sibships and to stress the genetic factor responsible for this anatomical defect.

Incidence and genetics of Legg-Perthes disease (osteochondritis deformans) in British Columbia: evidence of polygenic determination.

Abstract: Legg-Perthes disease (osteochondritis deformans) is an aseptic necrosis of the capital femoral epiphysis. The clinical and radiographic features of Legg-Perthes disease have been well documented (Goff, Shutkin, and Hersey, 1954; Kemp and Boldero, 1966) but apart from Molloy and MacMahon's Massachusetts study (1966) few epidemiologic investigations have been reported. A genetic component to the disease has been suggested by many authors (Goff et al, 1954; Goff, 1962) but the extent of familial occurrence and mode of inheritance have not been defined. The objectives of this study were twofold: firstly, to determine the incidence of Legg-Perthes in the Province of British Columbia, Canada, by identifying all children in whom the diagnosis was made for the first time during the period 1952-67 inclusive; secondly, to analyse for possible genetic factors.

Haemoglobin Q India (alpha 64(E13) aspartic acid histidine) associated with beta-thalassemia observed in three Sindhi families.

Abstract: Haemoglobin Q was first reported in a Chinese man in whom it was associated with Hb H disease, and therefore with a-thalassaemia (Vella et al, 1958). It has been discovered in other people, mostly in south-east Asia, and these reports have been summarized by Sagnet et al (1968). Although it was known that Hb Q was an a-chain abnormal haemoglobin with a mutation in the tryptic peptide No. 9 of the a-chain (aTpIX) which comprises residues 62-90 of the 141 residues of the a-chain, the exact amino-acid substitution had remained undetermined. However, 2 haemoglobins Q were characterized by Lorkin et al in 1970. One type came from both a Chinese and a Thai family (in which it was associated with a-thalassaemia) and had the substitution a74 Asp->His, and the other, a75 Asp--His, came from Iran. Independently, the first variant, described as Hb G Taichung, was found in a Chinese by Blackwell and Liu (1970), and in a Thai, where it was again associated with a-thalassaemia, as Hb Mahidol, by Pootrakul and Dixon (1970). In India only a few cases of Hb H disease have been found, indicating that a-thalassaemia is probably rare; f-thalassaemia is however quite common (Chatterjea, 1966; Chouhan, Sharma, and Parekh, 1970). We have recently observed 3 Sindhi-speaking Hindu families with children suffering from f,thalassaemia major. Family studies showed some members with /-thalassaemia minor and one with /3-thalassaemia major associated with Hb Q. This was shown to arise from an amino-acid substitution a64 Asp-->His, and was therefore different both from the Q Thailand (<74 Asp-->His) and Q Iran (a75 Asp->His). A preliminary report of this new Hb Q

Mongolism and sex: a common problem of cell proliferation?

Abstract: It is now evident that variations in chromosome constitution may have a profound effect on physical and mental development, both normal and pathological. Mongolism is the best known example of a severe congenital abnormality caused by the presence of an additional chromosome; while a difference in the sex chromosome constitution-XY in the male and XX in the female-produces the most far-reaching normal variation in human beings and other animal species. In spite of the spectacular progress in our knowledge of human chromosomes during the past 15 years, there is as yet no working hypothesis relating cause and effect; in other words, we need an answer to the question: 'By what mechanism do different chromosome constitutions result in different end products of development?'

A 45,XX,21--child: attempt at a cytological and clinical interpretation of the karyotype.

Abstract: A non-satellited, slightly submetacentric chromosome replacing one of the members of the 13-15 group was found in the apparently healthy father, paternal uncle, and sister; their karyotypes were otherwise normal. The aberrant chromosome is interpreted as being a result of pericentric inversion. One of the D chromosomes of the propositus was abnormally large and is assumed to represent duplication of a part of the long arm as a result of single crossover during meiosis in the father.

Rural-urban differentials in consanguinity.

Abstract: Parental consanguinity has been implicated in the manifestation of traits considered to have been transmitted through recessive genes and in some of the causes of perinatal morbidity and mortality (Stern, 1960). The latter aspect, however, needs further investigation. India, particularly the southern part, ranks among the top few countries where there is still a marked preference for consanguineous marriages and thus affords an opportunity to delineate the risks associated with inbreeding. It is also important to identify any changes towards preference of consanguineous marriages in view of the increasing urbanization or emancipation in a developing country. A previous study in an urban area (Rao, Inbaraj, and Kaliaperumal, 1971) estimated the proportion of consanguineous marriages to be 30-1% of all marriages. Indications that this frequency would be higher in the rural areas were suggested in a study of one village by Centerwall et al (1969). Detailed analyses for rural areas on the extent of consanguinity, types preferred, and their relationship to specific demographic factors have not been reported so far. In an attempt to investigate the correlates of infant mortality, a longitudinal research project was begun in 1969 covering large samples of urban and rural areas. As part of the base-line data, information on parental consanguinity was also obtained. In this paper the differential rates of consanguineous marriages in the urban and rural areas are described and discussed in relation to specific demographic characteristics.

A case of partial 14 trisomy 47,XY,(14q-)+ and translocation t(9p+;14q-) in mother and brother.

Abstract: adrenals. Autoradiography of skin fibroblast culture demonstrated that the cell line with 48 chromosome included a distinctly late-labelled X chromosome and an extra D chromosome labelling as expected for No. 13. The labelling in the 47 chromosome cell line also confirmed the extra D to be No. 13. No euploid cells were found. Chromosome analysis of peripheral blood from each parent was normal.

X-linked mental retardation without physical abnormality (Renpenning's syndrome) in sibs in an institution.

Abstract: A number of families have been reported in which mental retardation appeared to be segregating as an X-linked recessive (Martin and Bell, 1943; Allan, Herndon, and Dudley, 1944; Losowsky, 1961; Renpenning et al, 1962; Dunn et al, 1962/1963; Neuhauser et al, 1969; Snyder and Robinson, 1969; Neuhauser and Zerbin-Rudin, 1970). We reported 5 such families (Turner, Turner, and Collins, 1971b) in which the moderately retarded males were distinguished by the fact that they showed no physical abnormality. The first family in which X-linked mental retardation was associated with a similar lack of physical stigmata in the affected males was described by Renpenning et al (1962) and a similar family study was later published by Dunn et al (1962/1963). On the basis of the observations that the affected males in these families showed no physical stigmata the histories of a group of moderately retarded males without physical stigmata were examined and it was found that 60% has either an affected brother or a family history compatible with an X-linked entity. It was proposed therefore that the absence of physical abnormality in a moderately retarded male was suggestive of an X-linked form of mental retardation and the eponym of Renpenning's syndrome was suggested (Turner et al, 1971b). In order to obtain substantiation of this observation the brother pairs with mental retardation in an institution were ascertained and their families were studied.

Familial cancer of the colon and rectum.

Abstract: A familial relationship between intestinal polyposis and the predisposition of polyposis to colonic cancer has been accepted since the publication in 1952/1953 of Dukes's paper. He collected information on every patient presenting at St Mark's Hospital with polyposis coli and investigated the family background in each case. He was able to study 41 families, trace 156 cases of polyposis, and 114 cases of cancer of colon and rectum in this group of families. Other diseases are known to predispose to the development of colonic and rectal cancer. The most clearly documented of these is ulcerative colitis in which a polygenic aetiology has been suggested (McConnell, 1966). Solitary colonic polyps have been considered by some recent authors (Woolf, Richards, and Gardner, 1955; Morson and Bussey, 1970) to have a familial relationship, and some of these polyps are regarded as precancerous. By contrast, the presence of a familial tendency to cancer of the colon has only rarely been reported (Kluge, 1964; Fielding, 1969). In postulating a familial predisposition to cancer of the colon, one must take into account that this is a common disease in the western world (accounting for 2 6% of all deaths in England and Wales in 1969 and 13-9% of all cancer deaths) and consequently the fact that several members of a family die of this disease may be purely coincidental. The present report concerns a large family in which the incidence of colonic cancer appears too great to be attributed to chance.

Normal male development with Y chromosome long arm deletion (Yq

Abstract: Allerdice, P., Miller, 0. J., Miller, D. A., Breg, W. R., Gendel, E., and Zelson, C. (1971). Familial translocation involving chromosomes 6, 14, and 20 identified by quinacrine fluorescence. Humangenetik, 13, 205-209. Breg, W. R. (1972). Quinacrine fluorescence for identifying metaphase chromosomes, with special reference to photomicrography. Stain Technology, 47, 87-93. Breg, W. R., Miller, 0. J., Miller, D. A., and Allerdice, P. W. (1972). Identifications of reciprocal translocation chromosomes by quinacrine fluorescence. American Journal of Diseases of Children, 123, 561-564. Br0gger, A. (1967). Translocations in Human Chromosomes, p. 110. Universitets Forlaget, Oslo. Caspersson, T., Lomakka, G., and Zech, L. (1971). The 24 fluorescence patterns of the human metaphase chromosomes-distinguishing characters and variability. Hereditas, Genetiskt Arkiv, 67, 89102. Chicago Conference: Standardization in Human Cytogenetics (1966). Birth Defects: Original Article Series, II, 2. The National Foundation-March of Dimes, New York. Ford, C. E. and Clegg, H. (1969). Reciprocal translocations. British Medical Bulletin, 25, 110-114. Giannelli, F. (1965). Autoradiographic identification of the D (1315) chromosome responsible for D1 trisomic Patau's syndrome. Nature, 208, 669-672. Hauschteck, E., Murset, G., Prader, A., and Biihler, E. (1966). Siblings with different types of chromosomal aberrations due to D/Etranslocation of the mother. Cytogenetics, 5, 281-293. Jacobsen, P., Dupont, A., and Mikkelsen, M. (1963). Translocation in the 13-15 group as a cause of partial trisomy and spontaneous abortion in the same family. Lancet, 2, 584-585. Miller, D. A., Allerdice, P. W., Miller, 0. J., and Breg, W. R. (1971). Quinacrine fluorescence patterns of human D group chromosomes. Nature, 232,24-27. Miller, J. R., Dill, F. J., Corey, M. J., and Rigg, J. M. (1970). A rare translocation (47,XY,t(2p ;21q + ),21 +) associated with Down's syndrome. Journal ofMedical Genetics, 7, 389-393. Murken, J. D., Bauchinger, M., Palitzsch, D., Pfeifer, H., Suschke, J., and Haendle, H. (1970). Trisomie D2 bei einem 21 jihrigen Madchen (47,XX,14 +). Humangenetik, 10, 254-268. Patau, K., Smith, D., Therman, E., Inhorn, S., and Wagner, H. P. (1960). Multiple congenital anomaly caused by an extra autosome. Lancet, 1, 790-793. Taylor, A. (1968). Autosomal trisomy syndromes: a detailed study of 27 cases of Edwards' syndrome and 27 cases of Patau's syndrome. Journal of Medical Genetics, 5, 227-252. Taylor, M. B., Juberg, R. C., Jones, B., and Johnson, W. A. (1970). Chromosomal variability in the D1 trisomy syndrome. American Journal of Diseases of Children, 120, 374-381.

Pericentric enversion of chromosome no. 13 in a large family leading to duplication deficiency causing congenital malformations in three individuals.

Abstract: Received 4 April 1972. * Cytogenetics Laboratory, Genetics Committee of the University of Iceland, Department of Pathology, Reykjavik, Iceland. t Paediatric Department, University Hospital Iceland; Home for the Mentally Retarded, K6pavogur; Paediatric Department, St Joseph's Hospital, Reykiavik, Iceland. t John F. Kennedy Instituttet, GI. Landevej 7-9, Copenhagen, Denmark. ** Faculty of Medicine, University of Calgary, Calgary 42, Alberta, Canada. duplication deficiency derived from a maternal Dgroup pericentric inversion. A female with secondary amenorrhoea, webbed neck, and kyphosis and a chromosome D pericentric inversion was reported by Cohen, Capraro, and Takagi (1966/1967). Crandall and Sparkes (1970) described a pericentric inversion in 9 members of a family, all of whom were phenotypically normal. In the family presented here (Fig. 1) 3 children had congenital malformations. Chromosome analysis could only be performed in 2 of them, both had abnormal karyotypes. Chromosome studies in the family showed that 14 phenotypically normal individuals had an abnormal karyotype which differed from that found in the 2 abnormal children.

Genetical investigations in dyslexia.

Abstract: Dyslexia is a specific developmental disorder which manifests itself in difficulty in learning to read despite educational instruction, adequate intelligence, and sociocultural opportunity. This disorder, which is frequently constitutional in origin, depends on fundamental cognitive disabilities. By means of the differential diagnosis we can separate those defects in reading and writing which can be explained by sensory disorders or by other somatic defects; by different grades of mental defect, lack of training caused by disease, and absence from school; by change in the teaching language; by a bilingual education, wrong teaching methods, a bad relationship between the pupil and the teacher etc. These cases are regarded as secondary disorders of reading or pseudodyslexia. The aetiopathogenesis of dyslexia has not been clearly elucidated up to this time. Some authors mention the defect in connection with central lesions in the region of the gyri angularis and supramarginalis. Bender (1938) localizes the lesion in the temporal lobe, regarding dyslexia as a functional disorder of the speech region. Rabinovitch (1954) differentiates primary and secondary affected cases and regards the defect as a developmental deficiency rather than the result of acquired cerebral damage. Orton (1937) takes the disorder to be a genetically conditioned functional variant in the development of the dominance of the hemispheres. Bronner (1917) connected congenital dyslexia with disorders of intrauterine development, birth injury, infections, and disorders of postnatal development. Gesell and Amatruda (1947) include reading disorders in the sequelae of minor cerebral damage. Kawi and Pasamanick (1959) proved that the appearance of dyslexia was influenced by factors which are genetically held to cause encephalopathies in children. Kucera et al (1961) estimated that disorders of reading and writing were the principal symptoms in 10% of cases of postnatal infective lesions (pertu'ssis, encephalitis, morbillosa,

Genetic heterogeneity for dystrophia myotonica.

Abstract: The analogy of the haemoglobinopathies suggests that at any gene locus there may be numerous different mutations which will have varied clinical effects. Also, there are now a number of examples in medicine of clinically similar conditions which may be caused by mutations at more than one locus. Genetic heterogeneity is likely to be the rule rather than the exception. It is, however, difficult to recognize that there is more than one genetic variant of a condition which, even within families, has such a varied clinical manifestation and age of onset as dystrophia myotonica. Nevertheless, in a recent study of 40 index patients and their families (Bundey, Carter, and Soothill, 1970; Renwick et al, 1971) there were indications from intra-familial resemblance in age of onset of the disease that there are at least 2 variants, though both are dominant conditions. The evidence is given in this paper.

Camptodactyly: occurrence in two new genetic syndromes and its relationship to other syndromes.

Abstract: The term camptodactyly was coined by Landouzy (1906) to describe a form of contractures of the fingers. The aetiology of this defect is heterogeneous; it may be either genetic or occur as a sporadic event of unknown cause (Gordon, Davies, and Berman, 1969). It is further known that several independent heritable disorders are associated with camptodactyly (Welch and Temtamy, 1966). Recently we have studied two separate families each of which presented with camptodactyly. The main constellation of findings in addition to camptodactyly were identical in the affected members of each family, but one family differed markedly from the other. Since we have been unable to find previous reports describing these observations they seem to represent two new genetic syndromes. The purposes of this communication will be to give a detailed clinical account of each syndrome and to discuss the possible significance and relationship of camptodactyly in various genetically determined conditions.

A family study of Fallot's tetralogy.

Abstract: This analysis concerns Fallot's tetralogy, a form of cyanotic congenital heart disease about which there is little information relating to the population of north east England, and attempts to assess the influence of familial and other variables possibly concerned in its aetiology. This disease of the heart is named after Fallot who described it in 1888, though it had been recognized as a clinical entity over 200 years previously (Stensen, 1671). Classically, the condition includes 4 features: pulmonary obstruction, ventricular septal defect, right ventricular hypertrophy, and dextroposition of the aorta. Physiologically the combination of a ventricular septal defect with an obstruction of the pulmonary outflow tract results in a predominantly right to left shunt. The degree of overriding of the aorta varies individually, but it is the size of the ventricular septal defect together with the degree of pulmonary obstruction which determines the severity and clinical picture. The classification of congenital heart disease in childhood produced by the International Society of Cardiology (Watson, 1970) recognizes this by including the tetralogy in the category 'ventricular septal defect with obstruction of the right ventricular outflow tract'.

The inheritance of dental traits in a Chinese population in the United Kingdom.

Abstract: Dental traits such as those of Carabelli or incisor shovelling have fascinated anthropologists and dentists for many years. This is probably because they are easily observed in both living and skeletal material and they show ethnic differences in frequency which might have a genetic basis. If, however, these traits are to be of any value their mode of inheritance must be understood and so some preliminary work was done on an existing Liverpool family study described by Bowden and Goose (1969). In this material the behaviour of one trait (Carabelli's) was followed. This trait is situated on the lingual aspect of the mesio-lingual cusp of the maxillary 1st and, to a lesser extent, 2nd and 3rd molars (Fig. 1). It may take the form of a pit, fissure, or cusp, and following Kraus (1951), 4 categories are noted; (a) no evidence of Carabelli's trait-smooth surface with the absence of pits or fissures, (b) pits or fissures, (cl) cusp without free tip, and (c2) cusp with free tip. It was found that the formerly suggested model of 2 allelic autosomal genes without dominance did not seem satisfactory and it was suggested that the inheritance might be multifactorial (Goose and Lee, 1971). Further dental traits were then examined but owing to the large number of missing or filled teeth in the parents no fully satisfactory data could be obtained. However another population (Chinese) was available in Liverpool which it was felt might not suffer so much from this problem and so it was decided to investigate them as well.

Dominant ectrodactyly and possible germinal mosaicism.

Abstract: The split-foot or 'lobster claw' deformity is a form of congenital absence of one or more digits (ectrodactyly) affecting the central rays of the hand and foot. It can be sporadic or inherited, and although autosomal recessive cases are known (Freire-Maia, 1971) most inherited cases are due to an autosomal dominant gene. A notably careful survey of the literature by Vogel (1957/1958) reveals that there are 2 types of dominant ectrodactyly. In type 1, the fundamental lesion is bilateral cleft foot, and the hands may be affected but never in the absence of the foot lesion (Lewis, 1909). Transmission is by an autosomal dominant gene, and skipping never occurs, ie, penetrance is 100%. In type 2 the lesion is much more variable. Some cases have typical cleft hands and feet, while others have only one deformed hand and normal feet. The most important feature is that the feet are not always affected. Transmission is again by an autosomal dominant gene, but skipping often occurs, and the expression of the gene is much more variable than in type 1. In this paper 3 new pedigrees of type 1 dominant ectrodactyly are reported, and germinal mosaicism may be a likely explanation in all 3 families.

Mosaicism with translocation: autoradiographic and fluorescent studies of an inherited reciprocal translocation t(2q+;14q-).

Abstract: The propositus was born on 12 July 1970 after a fullterm gestation. The father was 26. The mother was 21 years old; she had previously had 3 consecutive firsttrimester spontaneous abortions. The amniotic fluid and the baby were both meconium stained. The umbilical cord was tightly coiled around his neck, and he required vigorous resuscitation. The Apgar score was 4 at 1 minute. At birth his weight was 2A4 kg, length 46 cm, head circumference 33 cm, chest circumference 33-5 cm. Dolichocephalic head, small palpebral fissures, right exotropia, retrocessed ears, increased nasolabial distance, upturned nares, cleft soft palate, large mouth, and micrognathia were noted (Fig. 1). Redundant skin was present over the lateral and posterior aspect of the neck. Flexion contractures of the proximal interphalangeal joints of the 3rd and 4th fingers were present bilaterally. The dermal ridges were hypoplastic. The dermatoglyphic patterns differed from his parents. He had 6 arches while his mother had one tented arch and his father had no arches. The fingernails were small. The pelvis was small and the hips were tight to abduction. No testis was palpable on the left and on the right it was felt in the inguinal canal. A left inguinal hernia was present. The infant had a weak, hoarse cry and had generalized hypertonia and hyperreflexia. During the first month of life intermittent episodes of tachypnoea, tachycardia, and cyanosis occurred. A grade III/VI harsh pansystolic murmur was heard. Heart failure was present and digitalis was administered until he was 4 months. At that time an electrocardiogram

Twin heritability study of the effect of corticosteroids on intraocular pressure.

Abstract: A glaucoma-like rise in intraocular pressure following prolonged use of cortisone was documented by Francois in 1954. Since then, the influence of glucocorticosteroid (steroid) eye drops on intraocular pressure has been studied extensively. Provocative testing of healthy eyes with topical steroid preparations has led to the characterization of a 'steroid response' consisting of a gradual rise in intraocular pressure when medication is instilled several times daily over a period of 4 to 6 weeks. When the topical steroid is discontinued the intraocular pressure returns to normal levels. Among groups of randomly selected subjects, steroid provocative testing evokes a heterogeneous response. Some subjects show a temporary glaucoma-like elevation of intraocular pressure, while others show little or no response. Frequency distributions of change in ocular pressure or of final pressure following a course of steroid provocation show a skew tailing towards the high end. On the basis of multimodal characteristics reported for sample frequency distributions, some investigators (Armaly, 1965; Armaly and Becker, 1965; Becker, 1971) have distinguished 3 subpopulations characterized by low, intermediate, and high levels of pressure response. An hypothesis has been advanced, based on population testing and family studies, that the hypertensive response to steroids is determined genetically by a simple autosomal mechanism (Armaly, 1966; Becker and Kolker, 1966; Becker, 1969). It is postulated that 3 distinct phenotypes can be identified by the level of pressure response and that these phenotypes correspond to the 3 possible genotypes of an allele pair, wherein one member of the pair determines a high level of response and the other member a low level of response. This genetic hypothesis holds pro-

ABO incompatibility as a cause of spontaneous abortion: evidence from abortuses.

Abstract: Although ABO incompatibility between mother and the conceptus has long been suspected as a cause of spontaneous abortion in man its precise contribution has not been completely resolved (Levene and Rosenfield, 1961). In spite of reports in which the incompatible mating was recognized to be a cause ofhabitual abortion (McNeil et al, 1954) and which eventually results in infertility (Behrman et al, 1960) or a reduction in the mean number of living children compared to the number in compatible matings (Matsunaga and Itoh, 1957/ 1958), such effects were not observed in other studies (Peritz, 1966/1967; Reed, 1968; Solish and Gerschowitz, 1969). Recently, Cohen (1970a) and Peritz (1971) reported a significantly higher fetal mortality in incompatible matings by a statistical analysis of complete reproductive data (ie, including stillbirths) and it has been assumed that the previous negative results might be due, at least in part, to limitation of the analysis to live births (Cohen, 1970a). In all of these reports data were analysed by comparing the fertility between compatible and incompatible matings, which were classified according to maternal and paternal blood types. To the best of our knowledge there has been only one report in which blood types of abortuses as well as the parents were examined, and the data were analysed on the basis of maternal-fetal incompatibility (Krieg and Kasper, 1968). These authors used the haemagglutination-inhibition technique to identify blood types of fresh fetal organs in a relatively small number of specimens, and no statistical analysis was described. According to the study of Coombs and his colleagues the mixed agglutination technique is the most sensitive and it is possible to identify the blood types of old, dried, or even fixed blood, and some other tissues by its application (Holborow et al, 1960; Coombs and Dodd, 1961). Since a large number of abortuses were available to us through an ongoing research project at the Vancouver General Hospital (Poland, 1968) we applied this technique to identify the blood type of spontaneously aborted fetuses with the purpose of estimating the maternalfetal ABO incompatibility as a cause of spontaneous abortion.

Christmas disease in one of a pair of monozygotic twin girls, possibly the effect of lyonization.

Abstract: The proposita, a girl of 18 months, was sent to our department in May 1970 from Jaszbereny County Hospital. She had been admitted previously on 2 occasions to the hospital for excessively severe bleeding following minor trauma. She was in severe shock both times and required multiple transfusions. After the 2nd episode she was transferred to us for further investigations. Her parents said that she always bruised easily after slight injury and developed sizeable swellings. There had been bleeding from the nose and gums on a few occasions. A swelling of the elbow joint was noted once, but it subsided spontaneously after a couple of weeks. We found her to be of average build and development. Several bruises were seen on her arms and legs. Her blood count was normal, without any gross anaemia present, probably as a result of her recent transfusions. There was no indication of organic disease on physical examination. No abnormality was found in the chest or abdomen. Musculature was adequately developed, joints appeared to be of normal shape and movements were unlimited in all extremities. She was a somewhat shy, but intelligent little girl.