Klinefelter's Syndrome Editors: H.-J. Bandmann and R. Breit Co-Editor: E. Perwein

With 82 Figures and 77 Tables

Springer-Verlag Berlin Heidelberg New York Tokyo 1984

Editors: Professor Dr. Hans-Jiirgen Bandmann Dr. Reinhardt Breit

Co-Editor: Dr. Elmar Perwein

Dermatologische und Allergologische Abteilung SUidtisches Krankenhaus Miinchen-Schwabing Kolner Platz 1,8000 Miinchen 40, FRO

ISBN-13: 978-3-540-13267-7

DOl: 10 .1007/97 8-3 -642-69644-2

e-ISBN-13: 978-3-642-69644-2

Library of Congress Cataloging in Publication Data. Main entry under title: Klinefelter's syndrome. Bibliography: p. Includes index. 1. Klinefelter's syn­drome-Addresses, essays, lectures. I. Bandmann, H.-J. (Hans-Jiirgen), 1923 -. II. Breit, R. (Reinhardt) III. Perwein. E. [DNLM: 1. Klinefelter's Syndrome. QS 677 K65] RC882.K59 1984 616'.042 84-10504

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Preface

Klinefelter's syndrome occurs relatively frequently, being diagnosed for one in 600 male infants, yet it is probably very rare that it is recognized early enough to make effective treatment possible. Often the person afflicted does not go to a doctor until physical and emotional disturbances have developed on the ba­sis of the syndrome. The appropriate therapy at the correct time can prevent many of these disturbances.

In our andrology outpatient clinic we encountered Klinefelter's syndrome almost three decades ago in patients suffering from impotentia generandi. It was not until later that we dealt with it in our capacities as dematologists. It was observed at a rate too high to be coincidental among younger men suffer­ing from ulcera crurum.

On the other hand, we failed to see the condition during our work as con­sultants in other specialities, especially internal medicine, although we re­peatedly attempted to identify it. We should have encountered it at least occa­sionally in our 10 years working in the Munich hospitals with their more than 4000 beds. It was this imbalance between the allegedly relative frequency of this condition and its rare detection which led us to plan a Klinefelter sympo­sium.

We soon determined, during a first search of the literature, that there was information in many more subject areas that we had expected or even guessed. Finally, thirty scientists (from the fields of anthropology, biochemistry, surge­ry, dermatology (and andrology), endocrinology, genetics (and cytogenetics), gynecology, immunology, orthodontics, clinical chemistry, pediatrics, patholo­gy, psychiatry (and child psychiatry), radiology, sexual psychology, and veteri­nary medicine) assembled in Murnau October 17-21, 1983; they came from Australia, Austria, Denmark, Germany, Holland, Italy, Mexico, Switzerland, the United Kingdom, and the United States.

It was a special pleasure to have Dr. Harry F. Klinefelter open the sympo­sium and to experience the knowledgeable interest with which he followed and discussed all the developments that have taken place since his first case studies in 1942.

Dr. G. Weiland (Organon Corporation) took care of all the preparations for the symposium and ensured an usually harmonious and fruitful atmosphere. We are grateful to all participants for the excellent cooperation which has made it possible to present the results of the symposium in book form.

VI Preface

We hope that the results of this symposium will contribute to enabling Kli­nefelter patients to lead the normal and happy lives they deserve, despite their genetic defects.

H.-J. Bandmann R. Breit

Harry F. Klinefelter was born in Baltimore, Maryland, in 1912. Mter premedi­cal training at the University of Virginia, he received his medical degree from the Johns Hopkins Medical School in 1937. The fifth year of his 6-year resi­dency training program at Johns Hopkins was spent in Boston, Massachusetts, at the Massachusetts General Hospital, working under Dr. Fuller Albright as a graduate assistant in medicine. Mter 3 years in the AUS, he began private prac­tice of internal medicine in Baltimore, where he continues to practice, affiliated with the Johns Hopkins and Union Memorial Hospitals. He is an Associate Professor of Medicine in the Johns Hopkins Medical School.

Syndrome Characterized by Gy­necomastia, Aspermatogenesis without A-Leydigism, and In­creased Excretion of Follicle­Stimulating Hormone!

HARRY F. KLINEFELTER, JR.,2 M.D., EDWARD C. REIFENSTEIN, JR., M.D. AND

FULLER ALBRIGHT, M.D. From the Medical Service of the Massachusetts Gen­eral Hospital and the Department of Medicine of the Harvard Medical School, Boston, Massachusetts

THE SYNDROME under discussion begins during adolescence and is characterized by gyneco­mastia and a very specific type of hypogonad­

ism. This latter is almost entirely in respect to the function of the tubular tissue (germinal epithelium and Sertoli cells) while the function of the Leydig cells (growth of phallus and prostate and of sexual hair) remains relatively normal. Thus one finds bilat­eral gynecomastia, small testes, aspermatogenesis, evidence of normal to moderately reduced function of the Leydig cells, increased excretion of follicle­stimulating hormone (FSH), and usually a reduced excretion of 17-ketosteroids. During the last 4 years, 7 cases have been observed in the clinics of the Massachusetts General Hospital; studies on these

Received for publication August,;, 1942. 1 The expense of these studies was partly defrayed by the Com­

mittee for Research in the Problems of Sex. of the National Re· search Council and the Macy Foundation.

2 Travelling Fellow, Johns Hopkins University Medical School. Read before the TwentY1sixth Annual Meeting of the Asscl

dation for the Study of Internal Secretions, Atlantic City, N. J., June 9, '942 .

Reprinted for private circulation from

THE JOURNAL OF CLINICAL ENDOCRINOLOGY

Vol. II, No. 11, November, 1942, pp. 615-627

Printed in U.S.A.

IT Gynecomastia]

patients and two additional private patients form the subject of this report.

REVIEW OF LITERATURE

Although these cases are not uncommon, few reports are found in the literature, and to our knowledge, no author has grouped them together as a definite clinical entity. Bedor in 1812, according to a later writer (1), de­scribed two brothers, 21 and 24 years old, with bilateral gynecomastia and small testes. Around 1840, several English authors (2-5) independently described a soldier, previously normal, who at the age of 53, developed small testes and gynecomastia a few months after trauma to the testes. The reports of this case vary in their details but the sequence of events seems to have been as stated. The development of gynecomastia in a previously normal en-year-old patient a few months after mumps orchitis was reported in ,877 (,). During the last 20 years, there have been several reports (5-9) of cases which possibly fit into this syndrome. Bronstein (10) in 1939 reported the only case, however, in which those hormone studies necessary for the diagnosis were carried out. This con­cerned a 17-year-old negro with gynecomastia of 5 years' duration. The testes were very small and there was a40-

Contents

H. F. Klinefelter Background, Recognition and Description of the Syndrome 1

E. Perwein Incidence of Klinefelter's Syndrome ......... . 8

K. D. Zang Genetics and Cytogenetics of Klinefelter's Syndrome 12

J. Murken and S. Stengel-Rutkowski Klinefelter's Syndrome in Prenatal Diagnosis: Incidence and Consequences for Genetic Counselling ......... 24

D. Knorr and J. Weil Klinefelter's Syndrome: Diagnostic Criteria in Childhood 29

S. G. Ratcliffe Klinefelter's Syndrome in Children - A Longitudinal Study of 47, XXX Boys Identified by Population Screening ........... 38

E. W. Jecht, K.-H. Conrad, and O. P. Hornstein The Clinical Appearance of Klinefelter's Syndrome

M. Horowitz, B. E. C. Nordin, J. Aaron, T. Steurer, R. M. Francis, J. C. Philcox, and R. Seamark Osteoporosis and Klinefelter's Syndrome

A. Barbarino, L. De Marinis, and A. Mancini Functional Characteristics of the Hypothalamic-Pituitary Unit in Klinefelter's Syndrome (Pituitary Hormone Release in Response to Exogenous Estradiol . . . . . . . . . . . . . . . . . . . . . . . . . .

R. Breit Lower Leg Ulcers in Klinefelter's Syndrome

B. Rossiwall Taurodontism in Klinefelter's Syndrome . .

P. Saldana-Garcia Dermatoglyphics of Klinefelter's Syndrome

48

51

62

71

80

85

X Contents

J. S. H. Tsung Immune Competence in Patients with Klinefelter's Syndrome ...... 101

D. Alarcon-Segovia and J. Sauza Systemic Lupus Erythematosus and Klinefelter's Syndrome 109

P. Meister Klinefelter's Syndrome and Testicular Tumors 115

o. Scheike, J. Vis/eldt, and B. Petersen Breast Carcinoma in Association with the Klinefelter's Syndrome 118

S. J. M. Muts-Homsma and J. P. M. Geraedts Klinefelter's Syndrome and Leukemia: Coincidence or Association? 127

H.-J. Bandmann and E. Perwein Histology of Testes in Klinefelter's Syndrome . . . . .

Chr. Sigg and Chr. Hedinger Ultrastructure of the Testis in Klinefelter's Syndrome

W.-B. Schill, R. Strasser, F. Krassnigg, W. Muller-Ester!, and E. Fink

131

137

Spermatological Investigations in Men with Klinefelter's Syndrome 147

H.-J. Vogt Sexual Behavior in Klinefelter's Syndrome 163

J. Nielsen and K. S@rensen The Importance of Early Diagnosis of Klinefelter's Syndrome 170

J. Martinius Psychiatric Aspects of Klinefelter's Syndrome in Adolescence 188

A. Roy Psychiatric Disorders in Relation to Klinefelter's Syndrome 192

E. Nieschlag Testosterone Substitution Therapy .................... 202

G. W. Rieck XXY Syndrome in Domestic Animals: Homologues to Klinefelter's Syndrome in Man .212

Subject Index ............... 224

List of Contributors

J. Aaron MRC Mineral Metabolism Unit, The General Infirmary, Leeds, United Kingdom

D. Alarcon-Segovia Department of Immunology and Rheumatology, Instituto Nacional de la Nutricion Salvador Zubinin, Calle Vasco de Quiroga 15, Delegacion Tlalpan, Mexico, D. F. 14000, Mexico

H. J. Bandmann Dermatologische und Allergologische Abteilung, Stadtisches Krankenhaus Miinchen-Schwabing, Keilner Platz 1, 8000 Miinchen 40, Federal Republic of Germany

A. Barbarino Institute of Internal Medicine, Division of Endocrinology, The Catholic University School of Medicine, Largo A. Gemelli 8, 00168 Rome, Italy

R. Breit Dermatologische und Allergologische Abteilung, Stadtisches Krankenhaus Miinchen-Schwabing, Keilner Platz 1, 8000 Miinchen 40, Federal Republic of Germany

K.-H. Conrad Dermatologische Klinik und Poliklinik der Universitat Erlangen-Niirnberg, Hartmannstrasse 14, 8520 Erlangen, Federal Republic of Germany

E. Fink Abteilung fUr Klinische Chemie und Klinische Biochemie, Universitat Miinchen, Nussbaumstra,sse 20, 8000 Miinchen 2, Federal Republic of Germany

R. M. Francis MRC Mineral Metabolism Unit, The General Infirmary, Leeds, United Kingdom

J. P. M. Geraedts Department of Internal Medicine, Division of Haematology, Leiden University Hospital, Rijnsburgerweg 10, 2333 AA Leiden, The Netherlands

XII List of Contributors

C. Hedinger Institut fUr Pathologie der UniversiHit Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland

o. P. Hornstein Dermatologische Klinik und Poliklinik der Universitat Erlangen-Nurnberg, Hartmannstrasse 14,8520 Erlangen, Federal Republic of Germany

M. Horowitz Department of Endocrinology, Royal Adelaide Hospital, North Terrace, Adelaide 5000, South Australia, Australia

E. W. Jecht Dermatologische Klinik und Poliklinik der Universitat Erlangen-Nurnberg, Hartmannstrasse 14,8520 Erlangen, Federal Republic of Germany

H. F. Klinefelter 550 North Broadway, Baltimore, MD 21205, USA

D. Knorr Kinderklinik der Universitat Munchen, Dr. von Haunersches Kinderspital, Lindwurmstrasse 4, 8000 Munchen 2, Federal Republic of Germany

F. Krassnigg Dermatologische Klinik und Poliklinik der Universitat Miinchen, Frauenlobstrasse 9-11, 8000 Munchen 2, Federal Republic of Germany

A. Mancini Institute of Internal Medicine, Division of Endocrinology, The Catholic University School of Medicine, Largo A. Gemelli 8, 00168 Rome, Italy

L. De Marinis Institute of Internal Medicine, Division of Endocrinology, The Catholic University School of Medicine, Largo A. Gemelli 8, 00168 Rome, Italy

J. Martinius Max-Planck-Institut fUr Psychiatrie, Kraepelinstrasse 10, 8000 Miinchen 40, Federal Republic of Germany P. Meister Institut fUr Pathologie, Stadtisches Krankenhaus Munchen-Harlaching, Akademisches Lehrkrankenhaus, Sanatoriumsplatz 2, 8000 Miinchen 90, Federal Republic of Germany

W. Miiller-Esterl Abteilung fUr Klinische Chemie und Klinische Biochemie, Universitat Munchen, Nussbaumstrasse 20, 8000 Munchen 2, Federal Republic of Germany

J. Murken Abteilung fUr Padiatrische Genetik, Kinderpoliklinik der Universitat Miinchen, Goethestrasse 29, 8000 Munchen 2, Federal Republic of Germany

S. J. M. Muts-Homsma Department of International Medicine, Division of Haematology, Leiden University Hospital, Rijnsburgerweg 10, 2333 AA Leiden, The Netherlands

List of Contributors XIII

J. Nielsen The Cytogenetic Laboratory, Arhus Psychiatric Hospital, 8240 Risskov, Denmark

E. Nieschlag Max-Planck-Gesellschaft, Klinische Forschungsgruppe fUr Reproduktionsmedizin, UniversiHi.ts-Frauenklinik, Steinfurter Strasse 107, 4400 Munster, Federal Republic of Germany

B. E. C. Nordin Department of Endocrinology, Royal Adelaide Hospital, North Terrace, Adelaide 5000, South Australia, Australia

E. Perwein Dermatologische und Allergologische Abteilung, SHidtisches Krankenhaus Munchen-Schwabing, KaIner Platz 1, 8000 Munchen 40, Federal Republic of Germany

B. Petersen Department of Radiology, Kommunehospitalet, Copenhagen, Denmark

J. C. Philcox Division of Clinical Chemistry, Institute of Medical and Veterinary Science, Adelaide, South Australia, Australia

S. G. Ratcliffe Medical Research Council, Clinical and Population Cytogenetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom

G. W. Rieck Justus-Liebig-Universitat Giessen, Institut fur Zuchthygiene und veterinarmedizinische Genetik, Hofmannstrasse 10, 6300 Giessen, Federal Republic of Germany

B. Rossiwall Brixnerstrasse 3, 6020 Innsbruck, Austria

A. Roy Department of Health and Human Services, Public Health Service, National Institutes of Health, Building 10, Room 4N214, Bethesda, MD 20205, USA

P. Saldana-Garcia The Kennedy-Galton Centre for Clinical Genetics, Harperbury Hospital, Harper Lane, Shenley, Radlett, Herts WS7 9HQ, United Kingdom

J. Sauza Department of Immunology and Rheumatology, Instituto Nacional de la Nutrici6n, Salvador Zubinin, Calle Vasco de Quiroga 15, Delegaci6n Tlalpan, Mexico, D. F. 14000, Mexico

O. Scheike The Radium Center, Finsen Institute, Strandboulevarden 49, 2100 Copenhagen, Denmark

XIV List of Contributors

W.-B. Schill Dermatologische Klinik und Poliklinik der UniversiHit Miinchen, Frauenlobstrasse 9-11, 8000 Miinchen 2, Federal Republic of Germany

R. Seamark Department of Obstetrics and Gynaecology, Queen Elizabeth Hospital, Adelaide, South Australia, Australia

Chr. Sigg Dermatologische Klinik und Poliklinik der Universitat Erlangen-Niirnberg, Hartmannstrasse 14,8520 Erlangen, Federal Republic of Germany

K. S0rensen The Cytogenetic Laboratory, Arhus Psychiatric Hospital, 8240 Risskov, Denmark

S. Stengel-Rutkowski Abteilung fiir Padiatrische Genetik, Kinderpoliklinik der Universitat Miinchen, Goethestrasse 29, 8000 Miinchen 2, Federal Republic of Germany

T. Steurer Department of Endocrinology, Royal Adelaide Hospital, North Terrace, Adelaide 5000, South Australia, Australia

R. Strasser Dermatologische Klinik und Poliklinik der Universitat Miinchen, Frauenlobstrasse 9-11, 8000 Miinchen 2, Federal Republic of Germany

J. S. H. Tsung Department of Pathology, Broadway Methodist Hospital, 8701 Broadway, Merriville, IN 46402, USA

J. Visfeldt Institute of Pathology, University of Copenhagen, Copenhagen, Denmark

H.-J. Vogt Dermatologische Klinik und Poliklinik der Technischen Universitat Miinchen, Biedersteiner Strasse 29, 8000 Miinchen 40, Federal Republic of Germany

J. Weil Kinderklinik der Universitat Miinchen, Dr. von Haunersches Kinderspital, Lindwurmstrasse 4, 8000 Miinchen 2, Federal Republic of Germany

K. D. Zang Institut fUr Humangenetik, Universitat des Saarlandes, Universitatskliniken, Bau 68, 6650 Homburg/Saar, Federal Republic of Germany