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Epidemiology of neuromuscular disorders in the under-20 population in Bologna province, Italy
Neuromusc.Disord.,Vol.2, No. 3, pp. 19%200,1992 Printed in Great Britain
0960-8966/92 $5.00 + 0.00 PergamonPressLtd
EPIDEMIOLOGY OF NEUROMUSCULAR DISORDERS IN THE UNDER-20 POPULATION IN BOLOGNA PROVINCE, ITALY LUCIANO MERLINI,*'~ SILVIA BONFIGLIOLI STAGNI,§ ELENA MARRI ~ and CLAUDIA GRANATA§ *Muscle Clinic and §Rehabilitation Unit of the Istituto Ortopedico Rizzoli, 40136 Bologna; and ~Osservatorio Epidemiologico, 40100 Bologna, Italy
(Received6 April 1992; revised 16 June 1992; accepted 19 June 1992)
Abstraet--A retrospective epidemiological survey of the principal neuromuscular disorders was undertaken in the population under the age of 20 yr in Bologna city and province. The incidence of Duchenne muscular dystrophy (DMD) proved to be 25.8 x 10-s, that is, comparable with the outcome of neonatal screening studies. The incidence of spinal muscular atrophy (SMA) was very high (11.2 x 10-5), probably the result of our greater awareness and recognition of this disorder. The prevalence of neuromuscular disorders in the 0-19 yr population is 1.5 times that in the general population; that of DMD is 28 × 10-5 vs 6.3 x 10-5 and that of the SMA 6.5 x 10-5 vs 1.2 x 10-5. Our results indicate that neuromuscular disorders, particularly DMD and SMA I and II, have a much higher prevalence in the first two decades of life than is generally thought. Awareness of the higher prevalence of neuromuscular disorders among the under-20s is essential to the adequate planning of medical services. Key words: Epidemiology, neuromuscular disorders, Duchenne muscular dystrophy, spinal muscular atrophy.
male population range from 1.9 to 9.5 x 10 -5 [4, 5]. There are no data on prevalence in the first two decades of life. Only one survey reports the inevitably higher prevalence rates for a population of school age [6]. For other neuromuscular disorders too the greatest medical need is in the first two decades of life, prevalence data for which are lacking. To quantify the need for these services it is important to know the number of individuals currently affected in a given territory. The aim of this survey is to estimate the incidence and prevalence rates of the commonest and most serious neuromuscular disorders in the population under the age of 20 yr in the Province of Bologna.
INTRODUCTION
Recent scientific advances in the field of neuromuscular disorders have fostered the expectation that the discovery of a cure, especially for the commonest and most serious of these disorders, Duchenne muscular dystrophy (DMD), is just round the corner. Until this hope materializes, however, all the orthopedic and rehabilitative treatments [1, 2] that prolong life and improve its quality for patients with neuromuscular disorders have to be provided. Vignos [1] stated that regular examination (at 2-3 monthly intervals) is essential to the management of contractures and to reduce the frequency of complications. The patients who need the most thorough and frequent examination, testing and treatment, both rehabilitative and surgical, are those with D M D . The majority of them die before the end of the second decade [3], usually from respiratory problems, and so the need for treatment facilities has to be quantified in relation to the population under the age of 20 yr. In the world literature the data on prevalence rates of D M D expressed in terms of the total tAuthor to whom correspondence should be addressed.
MATERIALS AND METHODS
The Province of Bologna is part of the EmiliaRomagna region of north-central Italy with a population on 31 December 1989 of 911,715, including 152,529 ( 1 6 . 7 % ) b o r n between 1970 and 1989 and hence under the age of 20 yr. Our survey covered the commoner hereditary neuromuscular diseases: Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), 197
198
L. MERLINI et al. Table 1. Number of cases of neuromuscular diseases identified among the children born and/or resident in the Province of Bologna in the period of 1970-1989 broken down by diagnosis
No. of cases
Percentage
26 4 2 2
33.8 5.2 2.6 2.6
18
23.4
25 77
32.4 100.0
Duchenne muscular dystrophy (DMD) Becker muscular dystrophy (BMD)
Myotonic dystrophy (MD) Facioseapulohumeral muscular dystrophy (FSHD) Spinal muscular atrophy (SMA) (I + II + III) Other neuromuscular diseases
Total
Table 2. Estimated annual incidences (x 10-5) at birth of the more common inherited neuromuscular diseases in the Province of Bologna, Italy, in the period 1970--1989 and data from the literature Province of Bologna No. of cases Population x 10 5
Duchenne muscular dystrophy Becker muscular dystrophy Spinal muscular atrophy (I + II + III) Spinal muscular atrophy (I) Spinal muscular atrophy (II)
20* 4 17¶[ 8 8
77,654t 77,654 150,97811 150,978 150,978
25.8 5.2 l 1.2
5.3 5.3
Literature
(x 10 ~) 24.3 5.5§ 6.0 ** 4.0-6.0tt 1.9 :~:~
* Out of the 26 cases identified 6 were born outside the province. t Number of live male births. :~ Estimated based on neonatal screening [8]. § Mostaeciuolo et aL [15]. ¶ Of the 18 cases identified 1 was born outside the province. IITotal number of live births (male + female). ** Winsor et al. [101. t t Emery [8]. ~: Mostacciuolo et aL 1121. Table 3. Estimated prevalences ( x 10- 5) of the more common inherited neuromuscular diseases in the Province of Bologna, Italy, in the population* under the age of 20 yr, and in the general populationt General
population Province of Bologna*
Neuromuscular disorders Duchenne muscular dystrophy~ Spinal muscular atrophy (I + II + III)
No. of cases
Residents
× 10 5
World surveyt (× 10 5)
64 22 10
152,529 78,460 152,529
42.0 28.0 6.5
28.6 6.3 1.2
* The data refer to patients with neuromuscular diseases living and resident in the Province of Bologna on 31 December 1989. t Emery [8]. :~ Expressed in terms of the male population.
myotonic dystrophy, facioscapulohumeral muscular dystrophy (FSHD) and childhood spinal muscular atrophy (SMA). All the other, rarer disorders are lumped together under the term "other neuromuscular diseases". The retrospective study was based on the case records of the pediatric and neurology services of the city's hospitals and of the school medical services for children born between 1970 and 1989. In Bologna city and province health care is organized in 10 area units, each with a network of outpatient clinics, nonuniversity and university hospitals (6.7 beds per 1000 in population), which report to a single central epidemiological observatory for data collection. All these facilities were involved in the survey through meetings and literature distribution. Their collaboration, which was total and effective, ensured complete
and exhaustive data collection. The information gathered was entered on preprinted forms provided for the purpose comprising three sections: identification data, clinical data, and laboratory data. The criteria of inclusion are the diagnostic criteria recommended by Dubowitz [7]. To assess the risk of disease we calculated the mean annual incidence per 100,000 (10 -5) live births only for early-onset neuromuscular disorders (DMD and SMA). In the case of X-linked disorders, such as DMD, the reference population is the male population, whereas for autosomal diseases, such as SMA, it is the whole population. The number of male live births in the communes of the province used for the calculation of incidence is an estimate of the true incidence, obtained from the aggregate number of births (the only available figure) assuming an
Epidemiology of NMD in the Under-20 Population
M : F birth ratio equal to that of births in the city of Bologna, figures for which were known. For the statistical analysis of incidence only cases born in Bologna city and its province (Province of Bologna) were included. To assess the frequency of the disorders under study we calculated the prevalence of neuromuscular diseases as a whole and of D M D and SMA in the population under the age of 20 resident in the Province of Bologna on 31 December 1989. RESULTS
Table 1 lists the diagnosis for the 77 cases of hereditary neuromuscular disease identified in the study. Table 2 gives the mean annual incidence rates o f the more common neuromuscular diseases. For D M D the incidence is 25.8 per 100,000 (10 -5) male live births, for SMA (I + II + III) as a whole 11.2 x 10 -5 live births. Table 3 gives the overall prevalence data for neuromuscular disorders, which in the Province of Bologna proved to be 42.0 per 100,000 inhabitants under the age of 20 yr, considering only those living and resident in the province on 31 December 1989. For D M D the prevalence rate is 28.0 per 100,000 male inhabitants under the age of 20, for SMA 6.5 x 10 -s inhabitants of both sexes under the age of 20 yr. DISCUSSION
In line with the published data, D M D proved to be the most common of the hereditary neuromuscular diseases. The incidence rate is comparable with the figure stated in the world literature (Table 2) which, based on population surveys, is 21.5 x 10 -5 male live births [3] while the one derived from various neonatal screening programs is 24.3 x 10 -5 [8]. Scheuerbrandt et al. [9] in a neonatal screening in Germany identified 48 affected out of 176,000 male live births, yielding an incidence of 27.2 x 10 -5. In our study 20 were affected out of 77,654 male live births which yields an incidence very close to 25.8 x 10 -5. The estimated incidence of SMA type I in our study is 5.3 x 10 -5 which tallies perfectly with that of around 40-60 x 10 -6 derived from the world literature by Emery in his review [8]. The incidence at birth of the three forms of SMA ranges, according to the literature, from nearly 6.0 x 10 -5 [10] to 8.0 x 10 -5 [11]. We found an
199
incidence at birth in our population of 11.2 x 10 -5. Our figure for SMA II was 5.3 x 10 -5, decidedly higher than the rate found by Mostacciuolo et al. [12] of 19.7 x 10 -6 (1.9 x 10 -5) live births (Table 2). It has to be said that while SMA type I is familiar to all neurologists and pediatricians and easy to diagnose, this is not so for SMA type II, partly because of the great confusion surrounding the clinical classification of this condition [13]. The attention paid to this particular form of SMA by the Istituto Ortopedico Rizzoli Muscle Clinic [14] may have led to greater awareness and recognition and hence to a higher estimation of its incidence. Reported prevalence rates of D M D , expressed in terms o f the total male population, range from 1.9 to 9.5 with a mean of around 6.3 x 10 -5 [4, 5, 8, 15]. The prevalence rate of 28.0 x 10 -5 males under 20 found in the Province of Bologna is nearly five times higher, a discrepancy that obviously depends on the age range on which the prevalence is based. While we calculated it on the population of under 20 yr, the period in which D M D is expected to be diagnosed and the patient to be still alive, the data usually reported measure prevalence on the total male population. In our view, this is deceptive because the Duchenne patient does not as a rule reach adulthood. Hence the prevalence data reported in the literature are misleading, giving the impression that the numerical weight of the disease is much lower than it actually is. The only survey that we are aware of that is comparable with our own is that of Bundey [6], who reports a prevalence rate of D M D of 24.4 x 10 -5 among schoolboys aged 516 yr. For the three forms of SMA taken together the prevalence rate in the Province of Bologna proved to be 6.5 x 10 -5. This is comparable with the figure given by Tangsrud and Halvorsen [16] for the child population of 4.2 x 10 -5, while in the general population SMA has a prevalence of around 1.2 x 10 -5 [8]. The intermediate and mild forms of SMA carry a shorter life expectancy than normal [13, 14] and so the calculation of prevalence with reference to the total population accentuates the false impression that this disease is extremely rare. In the Province of Bologna the prevalence of neuromuscular disorders as a whole proved to be 42.0 x 10 -5 in the population of under-20s. In the general population the estimation of neuromuscular patients is only 28.6 x 10 -5 [8]. Our study shows that neuromuscular disorders, particularly D M D and SMA I and II,
200
L. MERLINI et al.
have a much higher prevalence in the first two decades of life than in the general population. Awareness of the epidemiological data relating to young patients with neuromuscular disorders is therefore enormously important for the purpose of the adequate planning of medical services, when one considers all the preventive, diagnostic and rehabilitative measures that each of these patients needs in the course of the disease in the first two decades of life. Acknowledgements--We wish to thank G. Ambrosioni, M. Bacchilega, M. G. Caccialupi, E. Cacciari, B. M. Carlozzo, F. Corsini, S. Di Ciommo, F. Gagiioppa, P. Giovanardi-Rossi, S. Liverani, E. Loperfido, M. Mastella, M. Minarelli, A. Musi, G. Paolucci and G. P. Salvioli for their help and for placing at our disposal the data in their possession as heads of the Child Services of Bologna City and Province, the University Clinic of Bologna, and The Pediatric Division of the Ospedale Maggiore of Bologna. The survey was financed with grants from the Istituto Ortopedico Rizzoli and from Telethon-Italy. REFERENCES
1. Vignos P J. Management of musculo-skeletal complications in neuromuscular diseases: limb contractures and the role of stretching, braces and surgery. Phys Med Rehabil State of the Art Rev 1988; 2: 509-536. 2. Merlini L, Granata C. Rehabilitation of children with muscle diseases. Curr Concepts Neurol Neurosurg 1990; 3: 738-741. 3. Emery A E H. Duchenne Muscular Dystrophy. Oxford: Oxford University Press, 1988. 4. Prot J. Genetic-epidemiological studies in progressive muscular dystrophy. J Med Genet 1971; 8: 90- 96.
5. Monckton G, Hoskin V, Warren S. Prevalence and incidence of muscular dystrophy in Alberta. Clin Genet 1982; 21: 19-24. 6. Bundey S. A genetic study of Duchenne muscular dystrophy in the West Midlands. JMedGenet 1981; 18:1-7. 7. Dubowitz V. Muscle Disorders in Childhood. London: Saunders, 1978. 8. Emery A E H. Population frequencies of inherited neuromuscular diseases. A world survey. Neuromusc Disord 1991; 1: 19-29. 9. Scheuerbrandt G, Lundin A, Lfvgren T, Mortier W. Screening for Duchenne muscular dystrophy: an improved screening test for creatine kinase in a blood sample spotted on paper. Muscle Nerve 1986; 9:11-23. 10. Winsor E J, Murphy E G, Thompson M W, Reed T E. Genetics of childhood spinal muscular atrophy. J Med Genet 1971; 8: 143-148. 11. Pearn J. Incidence, prevalence, and gene frequency studies of chronic childhood spinal muscular atrophy. Helv Paediatr Acta 1978; 15: 409-413. 12. Mostacciuolo M L, Muller E, Trevisan C, Danieli G A. Epidemiology of SMA in northern east of Italy. Ital J Neurol Sci 1990; 98: 202. 13. Dubowitz V. Chaos in classification of the spinal muscular atrophies of childhood. Neuromusc Disord 1991; 1: 77-80. 14. Merlini L, Granata C, Capelfi T, Mattutini P, Colombo C. Natural history of infantile and childhood spinal muscular atrophy. In: Merlini L, Granata C, Dubowitz V, eds. Current Concepts in Childhood Spinal Muscular Atrophy. Wien, New York, Bologna: Springer & Aulo Gaggi, 1989: 95-100. 15. Mostacciuolo M L, LombardiA, Cambissa V, Danieli G A, Angelini C. Population data on benign and severe forms ofX - linked muscular dystrophy. Hum Genet 1987; 75: 217-220. 16. Tangsrud S E, Halvorsen S. Child neuromuscular disease in Southern Norway. Prevalence, age and distribution of diagnosis with special reference to "nonDuchenne muscular dystrophy". Clin Genet 1988; 34: 145-152.
0960-8966/92 $5.00 + 0.00 PergamonPressLtd
EPIDEMIOLOGY OF NEUROMUSCULAR DISORDERS IN THE UNDER-20 POPULATION IN BOLOGNA PROVINCE, ITALY LUCIANO MERLINI,*'~ SILVIA BONFIGLIOLI STAGNI,§ ELENA MARRI ~ and CLAUDIA GRANATA§ *Muscle Clinic and §Rehabilitation Unit of the Istituto Ortopedico Rizzoli, 40136 Bologna; and ~Osservatorio Epidemiologico, 40100 Bologna, Italy
(Received6 April 1992; revised 16 June 1992; accepted 19 June 1992)
Abstraet--A retrospective epidemiological survey of the principal neuromuscular disorders was undertaken in the population under the age of 20 yr in Bologna city and province. The incidence of Duchenne muscular dystrophy (DMD) proved to be 25.8 x 10-s, that is, comparable with the outcome of neonatal screening studies. The incidence of spinal muscular atrophy (SMA) was very high (11.2 x 10-5), probably the result of our greater awareness and recognition of this disorder. The prevalence of neuromuscular disorders in the 0-19 yr population is 1.5 times that in the general population; that of DMD is 28 × 10-5 vs 6.3 x 10-5 and that of the SMA 6.5 x 10-5 vs 1.2 x 10-5. Our results indicate that neuromuscular disorders, particularly DMD and SMA I and II, have a much higher prevalence in the first two decades of life than is generally thought. Awareness of the higher prevalence of neuromuscular disorders among the under-20s is essential to the adequate planning of medical services. Key words: Epidemiology, neuromuscular disorders, Duchenne muscular dystrophy, spinal muscular atrophy.
male population range from 1.9 to 9.5 x 10 -5 [4, 5]. There are no data on prevalence in the first two decades of life. Only one survey reports the inevitably higher prevalence rates for a population of school age [6]. For other neuromuscular disorders too the greatest medical need is in the first two decades of life, prevalence data for which are lacking. To quantify the need for these services it is important to know the number of individuals currently affected in a given territory. The aim of this survey is to estimate the incidence and prevalence rates of the commonest and most serious neuromuscular disorders in the population under the age of 20 yr in the Province of Bologna.
INTRODUCTION
Recent scientific advances in the field of neuromuscular disorders have fostered the expectation that the discovery of a cure, especially for the commonest and most serious of these disorders, Duchenne muscular dystrophy (DMD), is just round the corner. Until this hope materializes, however, all the orthopedic and rehabilitative treatments [1, 2] that prolong life and improve its quality for patients with neuromuscular disorders have to be provided. Vignos [1] stated that regular examination (at 2-3 monthly intervals) is essential to the management of contractures and to reduce the frequency of complications. The patients who need the most thorough and frequent examination, testing and treatment, both rehabilitative and surgical, are those with D M D . The majority of them die before the end of the second decade [3], usually from respiratory problems, and so the need for treatment facilities has to be quantified in relation to the population under the age of 20 yr. In the world literature the data on prevalence rates of D M D expressed in terms of the total tAuthor to whom correspondence should be addressed.
MATERIALS AND METHODS
The Province of Bologna is part of the EmiliaRomagna region of north-central Italy with a population on 31 December 1989 of 911,715, including 152,529 ( 1 6 . 7 % ) b o r n between 1970 and 1989 and hence under the age of 20 yr. Our survey covered the commoner hereditary neuromuscular diseases: Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), 197
198
L. MERLINI et al. Table 1. Number of cases of neuromuscular diseases identified among the children born and/or resident in the Province of Bologna in the period of 1970-1989 broken down by diagnosis
No. of cases
Percentage
26 4 2 2
33.8 5.2 2.6 2.6
18
23.4
25 77
32.4 100.0
Duchenne muscular dystrophy (DMD) Becker muscular dystrophy (BMD)
Myotonic dystrophy (MD) Facioseapulohumeral muscular dystrophy (FSHD) Spinal muscular atrophy (SMA) (I + II + III) Other neuromuscular diseases
Total
Table 2. Estimated annual incidences (x 10-5) at birth of the more common inherited neuromuscular diseases in the Province of Bologna, Italy, in the period 1970--1989 and data from the literature Province of Bologna No. of cases Population x 10 5
Duchenne muscular dystrophy Becker muscular dystrophy Spinal muscular atrophy (I + II + III) Spinal muscular atrophy (I) Spinal muscular atrophy (II)
20* 4 17¶[ 8 8
77,654t 77,654 150,97811 150,978 150,978
25.8 5.2 l 1.2
5.3 5.3
Literature
(x 10 ~) 24.3 5.5§ 6.0 ** 4.0-6.0tt 1.9 :~:~
* Out of the 26 cases identified 6 were born outside the province. t Number of live male births. :~ Estimated based on neonatal screening [8]. § Mostaeciuolo et aL [15]. ¶ Of the 18 cases identified 1 was born outside the province. IITotal number of live births (male + female). ** Winsor et al. [101. t t Emery [8]. ~: Mostacciuolo et aL 1121. Table 3. Estimated prevalences ( x 10- 5) of the more common inherited neuromuscular diseases in the Province of Bologna, Italy, in the population* under the age of 20 yr, and in the general populationt General
population Province of Bologna*
Neuromuscular disorders Duchenne muscular dystrophy~ Spinal muscular atrophy (I + II + III)
No. of cases
Residents
× 10 5
World surveyt (× 10 5)
64 22 10
152,529 78,460 152,529
42.0 28.0 6.5
28.6 6.3 1.2
* The data refer to patients with neuromuscular diseases living and resident in the Province of Bologna on 31 December 1989. t Emery [8]. :~ Expressed in terms of the male population.
myotonic dystrophy, facioscapulohumeral muscular dystrophy (FSHD) and childhood spinal muscular atrophy (SMA). All the other, rarer disorders are lumped together under the term "other neuromuscular diseases". The retrospective study was based on the case records of the pediatric and neurology services of the city's hospitals and of the school medical services for children born between 1970 and 1989. In Bologna city and province health care is organized in 10 area units, each with a network of outpatient clinics, nonuniversity and university hospitals (6.7 beds per 1000 in population), which report to a single central epidemiological observatory for data collection. All these facilities were involved in the survey through meetings and literature distribution. Their collaboration, which was total and effective, ensured complete
and exhaustive data collection. The information gathered was entered on preprinted forms provided for the purpose comprising three sections: identification data, clinical data, and laboratory data. The criteria of inclusion are the diagnostic criteria recommended by Dubowitz [7]. To assess the risk of disease we calculated the mean annual incidence per 100,000 (10 -5) live births only for early-onset neuromuscular disorders (DMD and SMA). In the case of X-linked disorders, such as DMD, the reference population is the male population, whereas for autosomal diseases, such as SMA, it is the whole population. The number of male live births in the communes of the province used for the calculation of incidence is an estimate of the true incidence, obtained from the aggregate number of births (the only available figure) assuming an
Epidemiology of NMD in the Under-20 Population
M : F birth ratio equal to that of births in the city of Bologna, figures for which were known. For the statistical analysis of incidence only cases born in Bologna city and its province (Province of Bologna) were included. To assess the frequency of the disorders under study we calculated the prevalence of neuromuscular diseases as a whole and of D M D and SMA in the population under the age of 20 resident in the Province of Bologna on 31 December 1989. RESULTS
Table 1 lists the diagnosis for the 77 cases of hereditary neuromuscular disease identified in the study. Table 2 gives the mean annual incidence rates o f the more common neuromuscular diseases. For D M D the incidence is 25.8 per 100,000 (10 -5) male live births, for SMA (I + II + III) as a whole 11.2 x 10 -5 live births. Table 3 gives the overall prevalence data for neuromuscular disorders, which in the Province of Bologna proved to be 42.0 per 100,000 inhabitants under the age of 20 yr, considering only those living and resident in the province on 31 December 1989. For D M D the prevalence rate is 28.0 per 100,000 male inhabitants under the age of 20, for SMA 6.5 x 10 -s inhabitants of both sexes under the age of 20 yr. DISCUSSION
In line with the published data, D M D proved to be the most common of the hereditary neuromuscular diseases. The incidence rate is comparable with the figure stated in the world literature (Table 2) which, based on population surveys, is 21.5 x 10 -5 male live births [3] while the one derived from various neonatal screening programs is 24.3 x 10 -5 [8]. Scheuerbrandt et al. [9] in a neonatal screening in Germany identified 48 affected out of 176,000 male live births, yielding an incidence of 27.2 x 10 -5. In our study 20 were affected out of 77,654 male live births which yields an incidence very close to 25.8 x 10 -5. The estimated incidence of SMA type I in our study is 5.3 x 10 -5 which tallies perfectly with that of around 40-60 x 10 -6 derived from the world literature by Emery in his review [8]. The incidence at birth of the three forms of SMA ranges, according to the literature, from nearly 6.0 x 10 -5 [10] to 8.0 x 10 -5 [11]. We found an
199
incidence at birth in our population of 11.2 x 10 -5. Our figure for SMA II was 5.3 x 10 -5, decidedly higher than the rate found by Mostacciuolo et al. [12] of 19.7 x 10 -6 (1.9 x 10 -5) live births (Table 2). It has to be said that while SMA type I is familiar to all neurologists and pediatricians and easy to diagnose, this is not so for SMA type II, partly because of the great confusion surrounding the clinical classification of this condition [13]. The attention paid to this particular form of SMA by the Istituto Ortopedico Rizzoli Muscle Clinic [14] may have led to greater awareness and recognition and hence to a higher estimation of its incidence. Reported prevalence rates of D M D , expressed in terms o f the total male population, range from 1.9 to 9.5 with a mean of around 6.3 x 10 -5 [4, 5, 8, 15]. The prevalence rate of 28.0 x 10 -5 males under 20 found in the Province of Bologna is nearly five times higher, a discrepancy that obviously depends on the age range on which the prevalence is based. While we calculated it on the population of under 20 yr, the period in which D M D is expected to be diagnosed and the patient to be still alive, the data usually reported measure prevalence on the total male population. In our view, this is deceptive because the Duchenne patient does not as a rule reach adulthood. Hence the prevalence data reported in the literature are misleading, giving the impression that the numerical weight of the disease is much lower than it actually is. The only survey that we are aware of that is comparable with our own is that of Bundey [6], who reports a prevalence rate of D M D of 24.4 x 10 -5 among schoolboys aged 516 yr. For the three forms of SMA taken together the prevalence rate in the Province of Bologna proved to be 6.5 x 10 -5. This is comparable with the figure given by Tangsrud and Halvorsen [16] for the child population of 4.2 x 10 -5, while in the general population SMA has a prevalence of around 1.2 x 10 -5 [8]. The intermediate and mild forms of SMA carry a shorter life expectancy than normal [13, 14] and so the calculation of prevalence with reference to the total population accentuates the false impression that this disease is extremely rare. In the Province of Bologna the prevalence of neuromuscular disorders as a whole proved to be 42.0 x 10 -5 in the population of under-20s. In the general population the estimation of neuromuscular patients is only 28.6 x 10 -5 [8]. Our study shows that neuromuscular disorders, particularly D M D and SMA I and II,
200
L. MERLINI et al.
have a much higher prevalence in the first two decades of life than in the general population. Awareness of the epidemiological data relating to young patients with neuromuscular disorders is therefore enormously important for the purpose of the adequate planning of medical services, when one considers all the preventive, diagnostic and rehabilitative measures that each of these patients needs in the course of the disease in the first two decades of life. Acknowledgements--We wish to thank G. Ambrosioni, M. Bacchilega, M. G. Caccialupi, E. Cacciari, B. M. Carlozzo, F. Corsini, S. Di Ciommo, F. Gagiioppa, P. Giovanardi-Rossi, S. Liverani, E. Loperfido, M. Mastella, M. Minarelli, A. Musi, G. Paolucci and G. P. Salvioli for their help and for placing at our disposal the data in their possession as heads of the Child Services of Bologna City and Province, the University Clinic of Bologna, and The Pediatric Division of the Ospedale Maggiore of Bologna. The survey was financed with grants from the Istituto Ortopedico Rizzoli and from Telethon-Italy. REFERENCES
1. Vignos P J. Management of musculo-skeletal complications in neuromuscular diseases: limb contractures and the role of stretching, braces and surgery. Phys Med Rehabil State of the Art Rev 1988; 2: 509-536. 2. Merlini L, Granata C. Rehabilitation of children with muscle diseases. Curr Concepts Neurol Neurosurg 1990; 3: 738-741. 3. Emery A E H. Duchenne Muscular Dystrophy. Oxford: Oxford University Press, 1988. 4. Prot J. Genetic-epidemiological studies in progressive muscular dystrophy. J Med Genet 1971; 8: 90- 96.
5. Monckton G, Hoskin V, Warren S. Prevalence and incidence of muscular dystrophy in Alberta. Clin Genet 1982; 21: 19-24. 6. Bundey S. A genetic study of Duchenne muscular dystrophy in the West Midlands. JMedGenet 1981; 18:1-7. 7. Dubowitz V. Muscle Disorders in Childhood. London: Saunders, 1978. 8. Emery A E H. Population frequencies of inherited neuromuscular diseases. A world survey. Neuromusc Disord 1991; 1: 19-29. 9. Scheuerbrandt G, Lundin A, Lfvgren T, Mortier W. Screening for Duchenne muscular dystrophy: an improved screening test for creatine kinase in a blood sample spotted on paper. Muscle Nerve 1986; 9:11-23. 10. Winsor E J, Murphy E G, Thompson M W, Reed T E. Genetics of childhood spinal muscular atrophy. J Med Genet 1971; 8: 143-148. 11. Pearn J. Incidence, prevalence, and gene frequency studies of chronic childhood spinal muscular atrophy. Helv Paediatr Acta 1978; 15: 409-413. 12. Mostacciuolo M L, Muller E, Trevisan C, Danieli G A. Epidemiology of SMA in northern east of Italy. Ital J Neurol Sci 1990; 98: 202. 13. Dubowitz V. Chaos in classification of the spinal muscular atrophies of childhood. Neuromusc Disord 1991; 1: 77-80. 14. Merlini L, Granata C, Capelfi T, Mattutini P, Colombo C. Natural history of infantile and childhood spinal muscular atrophy. In: Merlini L, Granata C, Dubowitz V, eds. Current Concepts in Childhood Spinal Muscular Atrophy. Wien, New York, Bologna: Springer & Aulo Gaggi, 1989: 95-100. 15. Mostacciuolo M L, LombardiA, Cambissa V, Danieli G A, Angelini C. Population data on benign and severe forms ofX - linked muscular dystrophy. Hum Genet 1987; 75: 217-220. 16. Tangsrud S E, Halvorsen S. Child neuromuscular disease in Southern Norway. Prevalence, age and distribution of diagnosis with special reference to "nonDuchenne muscular dystrophy". Clin Genet 1988; 34: 145-152.