American Journal of Medical Genetics 41:263-264 (1991)
Corresponding Editor’s Column
A Plea From So-called “Eastern-Europe” Andrew E. Czeizel Department of Human Genetics and Teratology, WHO Collaborating Centre, 1966 Budapest, Gyali ut 2-6, Hungary
In an effort to improve the state of medical genetics in Hungary, we confront not only the tasks of the present and the outlook for the future but also the achievements of the past. In this connection two kinds of comments seem indicated-one political and the other historical. It seems appropriate to clarify the term “Eastern Europe,” at least with respect to Czecho and Slovakia and Hungary. These two countries, in fact, are not Eastern European, but rather Central European countries. Geographically the borders of Central Europe are the Rhine river and Alps in the West, the North and Baltic seas in the North, the Vistula and Bug rivers and the Eastern Carpathian Mountains in the East, and the southern continuation of the Carpathian Mountains and Szava river in the South. Thus, Central Europe also includes parts of Poland and Rumania. Eastern Europe refers to the lands between the eastern border of Central Europe and the Western border of Asia (Ural Mountains). It must be remembered that before its decline in recent decades, Hungary and Czecho and Slovakia had outstanding traditions of medicine, especially a t the universities of Budapest and Prague. At a time of enthusiastic East-West solidarity and renewed collaboration it would be well to remember the many outstanding contributions made by these scientists of the recent past and t o acknowledge their priority, if appropriate. Three examples must suffice to illustrate these contributions and priorities. In 1881 Warren Tay, English ophthalmologist, reported on the symmetrical changes in the region of the yellow (now referred to as a central cherryred) spot with a gray-white area in a brother and sister. In 1887 Bernard Sachs, an American neurologist, described the arrested cerebral development with special reference to the cortical pathology of this disease in infants. Later Sachs recognized the conspicuous swelling of the neurons, the characteristic intraneuronal alteration, and the familial cluster in this uniform clinical pattern named amaurotic familial idiocy. However, it was Karoly (Karl) Shaffer (1864-19391, Professor of Neurology and Psychiatry at Budapest University [Haymaker, 19701,who gave an exact histopathological description of the disease and who characterized it as the first inborn error of lipid metabolism between 1902 and
Received for publication February 5, 1991.
0 1991 Wiley-Liss, Inc.
1907. His results were published in some German papers [1902,1905a,b, 1906a,b, 19071. In the first decade of this century the number of the Askhenazi Jewish community was about 910,000 in Hungary. As Schaffer wrote: “Chronologicallythe first aim was to define the exact anatomical substratum of the Tay-Sachs disease; the further and second aim was to read from the discovered histopathological alterations the causal factors dominating the pathological process, in other words to define the pathogenesis of the affection.” He first used the Bielschowsky silver impregnation method because “this method shows the outlines of the neurons as shapes drawn with Indian ink and so we can display precisely the big globular or bottle-shaped swelling of the neuron dendrites. The disproportional size of these local swellings, since the dentrite bloats to 10-20 times its normal thickness, automatically raises the question: what do they contain? This question was answered in 1907by my Weigert’s hematoxylin specimens for staining the medullary envelope, discovering that there are in these local swellings globules that vividly stain with Weigert’s hematoxylin. The size of these globules and their number showed a characteristic “quantitative expansion.” This cellular alteration was called the Schaffer’s cell or Schaffer’s cellular process in the literature. However, the most important citation from Schaffer is: “Hematoxylin stain means that since only lecithin is stained from among the components of myelinated fibres, these intracellular globules are of lecithinoid nature as I had named them.” In our opinion, this finding proves that Schaffer delineated the first inborn error of lipid metabolism. Later, Schaffer dealt a lot with the nosology of Tay-Sachs disease. On the one hand, Schaffer [19221clinically and genetically differentiated three clinical forms of “familial amaurotic idiocy,” i.e., infantile (Tay-Sachs),juvenile (Vogt-Spielmeyer),and adult (Kufs) based on their different cerebral localization and on different lipid composition. On the other hand, Schaffer differentiated Tay-Sachsdisease from Niemann-Pick disease based on their different histopathological and genetic manifestations. At that time, these distinct disease entities were considered only different clinical manifestations of the same disorder. Thus, Schaffer was one of the pioneers at “splitting” of clinically similar, but pathogenetically different disease entities. These facts explain why, in the past, Tay-Sachs disease was referred to as Tay-Sachs-Schafferdisease in the German litera-
264
Czeizel
ture. It would be correct to use this eponymic denomination again. Thomas Matolcsy (1901-1965), a surgeon in Budapest, described an interesting family in a leading German surgical periodical in 1936. The parents were healthy and nonconsanguineous;the mother had 6 pregnancies. The first two pregnancies ended in stillbirth with a birth weight over 2,500 g and without congenital abnormalities. The third girl died some hours after her birth. The cause of the death was not mentioned, but the lack of congenital abnormalities was stressed. The outcome of the next 3 pregnancies was infants affected with the multiple pterygium syndrome. All of them had severe pterygia of neck, axillae, antecubital, popliteal (from the gluteal region to the tendo calcaneus), and digital (it seemed to occur as syndactyly among all fingers) areas with secondary joint contractures. The eldest propositus died 1 month after his birth due to a secondary respiratory impairment. This was the most severe manifestation of this syndrome within this family. The surviving boy, age 13 years and girls, age 10, had similar patterns of severe webbing,though its manifestation was more severe in the boy. His secondary scoliosis and chest deformity were not associated with any primary abnormalities of vertebrae, ribs, or sternum in the X-ray photo. The boy had cryptorchidism. Matolcsy reviewed the literature and evaluated 53 reported cases with pterygium. He differentiated the entities of pterygium colli, popliteal pterygium, antecubital pterygium, and pterygium of axillae but he was not able to find a disorder similar to that observed in this family. Thus, his result was to delineate a new syndrome of autosomal recessive origin and to report his surgical method. Gorlin (1974) acknowledged that these cases were the first description of the multiple pterygium syndrome or pterygium syndrome and the catalogs of McKusick (1990):“The Mendelian Inheritance in Man” mentioned his name in this item (No. 265000). Therefore, it would be fair to call this syndrome “Matolcsytype multiple pterygium syndrome” in order to differentiate it from the lethal multiple pterygium syndrome (No. 253290). Erno (Ernst) Emil Moravcsik (1858-19241, a neurologist and professor at the Psychiatric Department of Budapest University, described a family with a special type of F’riedreich ataxia in 1904in the Hungarian Medical Weekly “Orvosi Hetilap” and his paper was reviewed in the well-known German Neurologisches Zentralblatt in 1904. Healthy and consanguineous first cousin parents had 3 affected children and one spontaneous abortion. Family history was unremarkable. All 3 children were mildly mentally retarded and short (18year-old girl, 146.5 cm; 19-year-oldbrother, 162 cm; and 23-year-old sister, 144.5 cm). Their neurological findings included dysarthria, ataxia, intention tremor, but normal sensation; the ophthalmologist found congenital cataracts, nystagmus, and strabismus. The oldest daughter had a pes equinovarus, kyphoscoliosis, and
had never menstruated. The boy had a mild kyphosis, his sexual development was not mentioned. The youngest daughter had a pes varus, a thoracic kyphosis, and one menstrual period at 11 years, but since then had been amenorrheic. Later, this autosomal recessive syndrome was described by Marinesco et al. [19311 and by Sjogren [19471. In 1956, F’ranceschetti et al. proposed to label this syndrome with the names of the senior authors of the above-mentioned papers, as MarinescoSjogren syndrome. Superneau et al. [19851declared that Moravcsik was the first who delineated this syndrome. Thus, it would be better to label this syndrome as Moravcsik-Marinesco-Sjogren syndrome.
REFERENCES Franceschetti A, Marty F, Klein D (1956): Un syndrome rare: Heredoataxia avec cataracte congenitale et retard mental. Confin Neurol 16:271-275. Gorlin R J (1974): Personal communication.Cited McKusick VA (1990): “Mendelian Inheritance in Man,” 9th ed. Baltimore: Johns Hopkins Univ. Press, p 1445. Haymaker W (ed) (1970): “The Founders of Neurology,” 2nded. Springfield, Ill: Charles C Thomas, pp 362-366. Marinesco G, Draganesco S, Vasilin D (1931): Nouvelle maladie familiale caracteriske par une cataracte congenitale et un arret du development somato-neuro-psychique. Encephale 26:97-109. Matolcsy T (1936): ijber die chirurgische Behandlung der angeborenen Flughaut. Arch Klin Chir 185:675-681. McKusick VA (1990): “Mendelian Inheritance in Man,” 9th ed. Baltimore: Johns Hopkins Univ. Press. Moravcsik E (1904): Friedreich-fele oroklott ataxia (Friedreich ataxia of genetic origin). Orvosi Hetilap 48. Suppl Neurol Psychiat 170-174. Reviewed in Neurol Zbl, Friedreich‘sche hereditare Ataxie. 23:949-950, 1904. Sachs B (1887): On arrested cerebral development with special reference to its cortical pathology. J Nerv Dis 14:541. Schaffer (1902): Uber einen Fall von Tay-Sachsscher amaurotischer Idiotie mit Befund. Wein Klin Rundschau 16:324-325. Schaffer A (1905a):Weitere Beitrage zur pathologischen Histologie der familiaren amaurotischen Idiotie. J Psychol Neurol 6234-102. Schaffer K (1905b): Zur Pathogenese der Tay-Sachsschen amaurotischen Idiotie. Neurol Zbl 24:386-437. Schaffer K (1906a): Ther Fibrillenbilder der progressiven Paralyse. Neurol Zbl 25:2-54. Schaffer K (1906b): Beitrage zur Nosolographie und Histopathologie der amaurotisch-paralytischen Idioteformen. Arch Psychiat 42:127-160. Schaffer K (1907): l h e r die Pathohistologie eines neuren Falles von Sachs’scher familiar-amaurotischer Idiotie mit einem Ausblick auf das Wesen der sogenannten Neurofibrillen. J Psychol Neurol 10:121-144. Schaffer K (1922): Tatsachlisches und Hypothetisches aus der Histopathologie der infantil-amaurotischen Idiotie. Arch Psychiat Nervenkr 64570-616. Sjogren T (1947): Hereditary congenital spinocerebellar ataxia combined with congenital cataract and oligophrenia. Acta Psychiat Neurol Scand 46(Suppl):286-289. Superneau D, Wertelecki W, Zellweger H (1985): The MarinescoSjogren syndrome described a quarter of a century before Marinesco. Am J Med Genet 22:647-648. Tay W (1881):Symmetrical changes in the region of the yellow spot in each eye ofan infant. Trans Ophthalmol Soc UK 155.cited Schaffer [19221.
Corresponding Editor’s Column
A Plea From So-called “Eastern-Europe” Andrew E. Czeizel Department of Human Genetics and Teratology, WHO Collaborating Centre, 1966 Budapest, Gyali ut 2-6, Hungary
In an effort to improve the state of medical genetics in Hungary, we confront not only the tasks of the present and the outlook for the future but also the achievements of the past. In this connection two kinds of comments seem indicated-one political and the other historical. It seems appropriate to clarify the term “Eastern Europe,” at least with respect to Czecho and Slovakia and Hungary. These two countries, in fact, are not Eastern European, but rather Central European countries. Geographically the borders of Central Europe are the Rhine river and Alps in the West, the North and Baltic seas in the North, the Vistula and Bug rivers and the Eastern Carpathian Mountains in the East, and the southern continuation of the Carpathian Mountains and Szava river in the South. Thus, Central Europe also includes parts of Poland and Rumania. Eastern Europe refers to the lands between the eastern border of Central Europe and the Western border of Asia (Ural Mountains). It must be remembered that before its decline in recent decades, Hungary and Czecho and Slovakia had outstanding traditions of medicine, especially a t the universities of Budapest and Prague. At a time of enthusiastic East-West solidarity and renewed collaboration it would be well to remember the many outstanding contributions made by these scientists of the recent past and t o acknowledge their priority, if appropriate. Three examples must suffice to illustrate these contributions and priorities. In 1881 Warren Tay, English ophthalmologist, reported on the symmetrical changes in the region of the yellow (now referred to as a central cherryred) spot with a gray-white area in a brother and sister. In 1887 Bernard Sachs, an American neurologist, described the arrested cerebral development with special reference to the cortical pathology of this disease in infants. Later Sachs recognized the conspicuous swelling of the neurons, the characteristic intraneuronal alteration, and the familial cluster in this uniform clinical pattern named amaurotic familial idiocy. However, it was Karoly (Karl) Shaffer (1864-19391, Professor of Neurology and Psychiatry at Budapest University [Haymaker, 19701,who gave an exact histopathological description of the disease and who characterized it as the first inborn error of lipid metabolism between 1902 and
Received for publication February 5, 1991.
0 1991 Wiley-Liss, Inc.
1907. His results were published in some German papers [1902,1905a,b, 1906a,b, 19071. In the first decade of this century the number of the Askhenazi Jewish community was about 910,000 in Hungary. As Schaffer wrote: “Chronologicallythe first aim was to define the exact anatomical substratum of the Tay-Sachs disease; the further and second aim was to read from the discovered histopathological alterations the causal factors dominating the pathological process, in other words to define the pathogenesis of the affection.” He first used the Bielschowsky silver impregnation method because “this method shows the outlines of the neurons as shapes drawn with Indian ink and so we can display precisely the big globular or bottle-shaped swelling of the neuron dendrites. The disproportional size of these local swellings, since the dentrite bloats to 10-20 times its normal thickness, automatically raises the question: what do they contain? This question was answered in 1907by my Weigert’s hematoxylin specimens for staining the medullary envelope, discovering that there are in these local swellings globules that vividly stain with Weigert’s hematoxylin. The size of these globules and their number showed a characteristic “quantitative expansion.” This cellular alteration was called the Schaffer’s cell or Schaffer’s cellular process in the literature. However, the most important citation from Schaffer is: “Hematoxylin stain means that since only lecithin is stained from among the components of myelinated fibres, these intracellular globules are of lecithinoid nature as I had named them.” In our opinion, this finding proves that Schaffer delineated the first inborn error of lipid metabolism. Later, Schaffer dealt a lot with the nosology of Tay-Sachs disease. On the one hand, Schaffer [19221clinically and genetically differentiated three clinical forms of “familial amaurotic idiocy,” i.e., infantile (Tay-Sachs),juvenile (Vogt-Spielmeyer),and adult (Kufs) based on their different cerebral localization and on different lipid composition. On the other hand, Schaffer differentiated Tay-Sachsdisease from Niemann-Pick disease based on their different histopathological and genetic manifestations. At that time, these distinct disease entities were considered only different clinical manifestations of the same disorder. Thus, Schaffer was one of the pioneers at “splitting” of clinically similar, but pathogenetically different disease entities. These facts explain why, in the past, Tay-Sachs disease was referred to as Tay-Sachs-Schafferdisease in the German litera-
264
Czeizel
ture. It would be correct to use this eponymic denomination again. Thomas Matolcsy (1901-1965), a surgeon in Budapest, described an interesting family in a leading German surgical periodical in 1936. The parents were healthy and nonconsanguineous;the mother had 6 pregnancies. The first two pregnancies ended in stillbirth with a birth weight over 2,500 g and without congenital abnormalities. The third girl died some hours after her birth. The cause of the death was not mentioned, but the lack of congenital abnormalities was stressed. The outcome of the next 3 pregnancies was infants affected with the multiple pterygium syndrome. All of them had severe pterygia of neck, axillae, antecubital, popliteal (from the gluteal region to the tendo calcaneus), and digital (it seemed to occur as syndactyly among all fingers) areas with secondary joint contractures. The eldest propositus died 1 month after his birth due to a secondary respiratory impairment. This was the most severe manifestation of this syndrome within this family. The surviving boy, age 13 years and girls, age 10, had similar patterns of severe webbing,though its manifestation was more severe in the boy. His secondary scoliosis and chest deformity were not associated with any primary abnormalities of vertebrae, ribs, or sternum in the X-ray photo. The boy had cryptorchidism. Matolcsy reviewed the literature and evaluated 53 reported cases with pterygium. He differentiated the entities of pterygium colli, popliteal pterygium, antecubital pterygium, and pterygium of axillae but he was not able to find a disorder similar to that observed in this family. Thus, his result was to delineate a new syndrome of autosomal recessive origin and to report his surgical method. Gorlin (1974) acknowledged that these cases were the first description of the multiple pterygium syndrome or pterygium syndrome and the catalogs of McKusick (1990):“The Mendelian Inheritance in Man” mentioned his name in this item (No. 265000). Therefore, it would be fair to call this syndrome “Matolcsytype multiple pterygium syndrome” in order to differentiate it from the lethal multiple pterygium syndrome (No. 253290). Erno (Ernst) Emil Moravcsik (1858-19241, a neurologist and professor at the Psychiatric Department of Budapest University, described a family with a special type of F’riedreich ataxia in 1904in the Hungarian Medical Weekly “Orvosi Hetilap” and his paper was reviewed in the well-known German Neurologisches Zentralblatt in 1904. Healthy and consanguineous first cousin parents had 3 affected children and one spontaneous abortion. Family history was unremarkable. All 3 children were mildly mentally retarded and short (18year-old girl, 146.5 cm; 19-year-oldbrother, 162 cm; and 23-year-old sister, 144.5 cm). Their neurological findings included dysarthria, ataxia, intention tremor, but normal sensation; the ophthalmologist found congenital cataracts, nystagmus, and strabismus. The oldest daughter had a pes equinovarus, kyphoscoliosis, and
had never menstruated. The boy had a mild kyphosis, his sexual development was not mentioned. The youngest daughter had a pes varus, a thoracic kyphosis, and one menstrual period at 11 years, but since then had been amenorrheic. Later, this autosomal recessive syndrome was described by Marinesco et al. [19311 and by Sjogren [19471. In 1956, F’ranceschetti et al. proposed to label this syndrome with the names of the senior authors of the above-mentioned papers, as MarinescoSjogren syndrome. Superneau et al. [19851declared that Moravcsik was the first who delineated this syndrome. Thus, it would be better to label this syndrome as Moravcsik-Marinesco-Sjogren syndrome.
REFERENCES Franceschetti A, Marty F, Klein D (1956): Un syndrome rare: Heredoataxia avec cataracte congenitale et retard mental. Confin Neurol 16:271-275. Gorlin R J (1974): Personal communication.Cited McKusick VA (1990): “Mendelian Inheritance in Man,” 9th ed. Baltimore: Johns Hopkins Univ. Press, p 1445. Haymaker W (ed) (1970): “The Founders of Neurology,” 2nded. Springfield, Ill: Charles C Thomas, pp 362-366. Marinesco G, Draganesco S, Vasilin D (1931): Nouvelle maladie familiale caracteriske par une cataracte congenitale et un arret du development somato-neuro-psychique. Encephale 26:97-109. Matolcsy T (1936): ijber die chirurgische Behandlung der angeborenen Flughaut. Arch Klin Chir 185:675-681. McKusick VA (1990): “Mendelian Inheritance in Man,” 9th ed. Baltimore: Johns Hopkins Univ. Press. Moravcsik E (1904): Friedreich-fele oroklott ataxia (Friedreich ataxia of genetic origin). Orvosi Hetilap 48. Suppl Neurol Psychiat 170-174. Reviewed in Neurol Zbl, Friedreich‘sche hereditare Ataxie. 23:949-950, 1904. Sachs B (1887): On arrested cerebral development with special reference to its cortical pathology. J Nerv Dis 14:541. Schaffer (1902): Uber einen Fall von Tay-Sachsscher amaurotischer Idiotie mit Befund. Wein Klin Rundschau 16:324-325. Schaffer A (1905a):Weitere Beitrage zur pathologischen Histologie der familiaren amaurotischen Idiotie. J Psychol Neurol 6234-102. Schaffer K (1905b): Zur Pathogenese der Tay-Sachsschen amaurotischen Idiotie. Neurol Zbl 24:386-437. Schaffer K (1906a): Ther Fibrillenbilder der progressiven Paralyse. Neurol Zbl 25:2-54. Schaffer K (1906b): Beitrage zur Nosolographie und Histopathologie der amaurotisch-paralytischen Idioteformen. Arch Psychiat 42:127-160. Schaffer K (1907): l h e r die Pathohistologie eines neuren Falles von Sachs’scher familiar-amaurotischer Idiotie mit einem Ausblick auf das Wesen der sogenannten Neurofibrillen. J Psychol Neurol 10:121-144. Schaffer K (1922): Tatsachlisches und Hypothetisches aus der Histopathologie der infantil-amaurotischen Idiotie. Arch Psychiat Nervenkr 64570-616. Sjogren T (1947): Hereditary congenital spinocerebellar ataxia combined with congenital cataract and oligophrenia. Acta Psychiat Neurol Scand 46(Suppl):286-289. Superneau D, Wertelecki W, Zellweger H (1985): The MarinescoSjogren syndrome described a quarter of a century before Marinesco. Am J Med Genet 22:647-648. Tay W (1881):Symmetrical changes in the region of the yellow spot in each eye ofan infant. Trans Ophthalmol Soc UK 155.cited Schaffer [19221.
