Population frequencies of inherited neuromuscular diseases—A world survey

Neuromuscular Disorders, Vol. I, No. I. pp. 19-29. 1991 Printed in Great Britain

POPULATION

0960-8966/91 $3.00 + 0.00 ~5) 1991 Pergamon Press pie

FREQUENCIES DISEASES--A

OF INHERITED WORLD

NEUROMUSCULAR

SURVEY

ALAN E. H. EMERY* European Neuromuscular Centre, Baarn, The Netherlands (Received 24 August 1990)

Abstraet--A survey of the world literature, involving over 150 reported studies, of the population frequencies of various inherited neuromuscular diseases has been carried out. Data are presented for the commoner forms of muscular dystrophy (Duchenne, Becker, facioscapuiohumeral, limb girdle), myotonic dystrophy and congenital myotonias, proximal spinal muscular atrophies, and the hereditary motor and sensory neuropathies. A conservative estimate of the overall prevalence among both sexes is around 286 x 10-6, that is I in 3500 of the population may be expected to have a disabling inherited neuromuscular disease presenting in childhood or in later life. If severe disorders manifest only in infancy and early childhood (e.g. Werdnig-Hoffmann disease and severe congenital muscular dystrophy) and the rare forms of dystrophy and myopathy are also included, then the overall prevalence could well exceed 1 in 3000.

INTRODUCTION

Definitions The t e r m p r e v a l e n c e is used for the number of

A survey o f the world literature on the population frequencies of various inherited neuromuscular diseases affecting children and adults has been carried out. It is hoped that this information will provide a useful reference base for future investigators working in this field. Such information may be valuable not only for estimating various genetic parameters, for example gene frequencies, but also in monitoring the effects o f any preventive measures, such as genetic counselling, as well as in planning for the welfare needs of the handicapped in the population. The last is attracting increasing attention from the medical and caring professions. There are many different hereditary disorders which affect the neuromuscular system [1] but most are very rare. Here only the more frequent disorders will be considered, including the c o m m o n e r forms o f muscular dystrophy and spinal muscular atrophy, myotonic dystrophy, the congenital myotonias, the hereditary m o t o r and sensory neuropathies, familial m o t o r neurone disease and familial myasthenia gravis.

affected individuals in the population at a particular point in time (point prevalence), or within a given period of time (period prevalence), in relation to the total number of individuals who are at risk at the time. In the case of an X-linked disorder the reference population would be the male population, but in the case of an autosomal disorder it would be the entire population. Since it is often unlikely that all affected individuals in a given population will be ascertained, the probability o f ascertainment (rr) has been taken into account in some studies [2] such that: P = A/rcN

where P = prevalence, A -- number of affecteds in the population and N = size of the population at risk. There are a number of ways of estimating rr [3, 4] perhaps the simplest being [5]: ~, a(a -

1)

E a(r -

1)

where summation is over all families and a = number of affecteds ascertained independently as probands and r = total number of affecteds.

* Address for correspondence: European Alliance of Muscular Dystrophy Associations, The Medical School, Universityof Edinburgh, Edinburgh EH8 9AG, U.K. 19

20

A. E. H. EMERY Table I, Duchenne muscular dystrophy: prevalence in the population and incidence in live male births (LMB) Prevalence

Country

Year

Affected

Total

Incidence x 10 "

Australia N.S.W. Victoria Western Canada Alberta Ontario Denmark Finland Helsinki Germany Dresden Dresden

1979

94

Fukuoka Kumamoto Shimane "Pooled d a t a " Libya Netherlands Groningen Norway

532,302 223,330 173,126

186 219 202

Cowan et al., (1980) [36] Lawrence et al., (19731 [37] Hurse & Kakulas, (1974) [38] Kakulas & Hurse, (19771 [39]

195(~74 1956-76 69.41" 1965-75

110

420,374

262 292 222

Monckton et al., 11982) [40] Williams et al., (1983) [41] Leth et aL, (1985) [42]

1965 80

29

122.595

237

Langetal.,(19891143]

1960,69 1970,79

26 25

145,99(I 117,650

178 213

1958 73 1918-32

51 2I

165,898 125,000

307 168

1963

1I

187,200

58.8

Kunath, (1983) [44] Kunath, (19831 [44] see also L6ssner & Wagner, (1987) [45] Spiegler & Herrmann, (1983) [46] Becker, (1980) [47] reported originally in 1955 Gudmundsson, (1968) [48]

1973 1973

9 39

353,382 655.840

25.5~ 59.5~

Kott et al., (19731 [49] Kott et al., (19731 [49]

1975

28

403,730

69.3

1975

126

3,771,329

33.4

1970 1980

85 106

2,498,422 3,335,577

34.0 31.8

1965

46

1983 1975 197982 1985

31 32 384

1983

468

1983

32

Poland Warsaw Rumania Switzerland Bern United Kingdom England (NE) England (NE)

1990

136 113 71

1949 58 1,800,000 17.2 768,876 41.6 1956-70 8,508,000 67.H 0z = 0.673) 60.0+

156 24 9 73 121 8 66 76

721,163 61,470 92,631 301,283 805,335 39,980 234,369 292,637

71

Nigro et al., (1983) [50] kucci, (1980) [51] Nigris, (1984) [52] Schiffer et al., (1981) [53] Ferrari et al., (1980) [541 Danieli, (19841 [55] Danieli, et al., (I 977) [56] Mostacciuolo et al.. (19871 [57]

217

Yasuda & Kondo, (1980) [6] Kuroiwa & Miyazaki, 11967) [58] Araki et al., (1987) [59] Takeshita et al., ( 19771 [32] Kanamori et al.. (1987) [60]

9

46A65

194

19

91,157

208 292

Radhak rishnan et al., (1987) [6 I] 1,420,962

251

van Essen & ten Kate, (1984) [62] Tangsrud & Halvorsen. ( 1988)[63]

1953 60 1961 68

46 214

328A 10 1,387,694

1411 154

Prot, (1971) [64] Radu & Sark6zi, (1978) [65]

1939 54

26

119,395

218

Moser et al. (19641 [66]

1940-46 1952-61 1962-71 1972-81

18 86 65 37

138,403 275,990 290,017 207,873

130 311 224 178

1939~49 1939~,9

7 15

46,210 105.310

151 142

Walton, (1955) [67] Gardner-Medwin & Sharpies. (1989) [68] Gardner-Medwin & Sharpies, (1989) [68] Blyth & Pugh, ( 19591 [69] Blyth & Pugh, (19591 [69]

1942-51 1953-68

28 47

153,692 177,413

182 265

Bundey, ( 1981 ) [70] Stevenson, (1958) [71] Brooks & Emery. (19771 [72]

293,833 108.9:~

3,300,000 3,130,000 3,070,000

41.2 36.1 23.1

110,434 244.5:~

220

5I 1 - • 51

216 390 97 242 150 200 282 260

357

7,102,598 65.9"~ 1963 74

27

196(~71 1951-75 1962 78 1955-74 1956,75 1960,75 1959 68 1959-68

1,343,167 49.9f (,,r= 0.686)

19.51"

1968 1979 1988 England (Midlands) Leeds West Riding England (Midlands) 1976 N. Ireland -Scotland (SE) U.S.A. Colorado Minnesota 1955 Utah Wisconsin 1959

Yugoslavia Ljubljana

× 10 ~ Reference

99 49 35

989,100 95.0f

1965

Affected TotaI(LMB)

1960-71 1957 63 1950,69

Erfurt Sudbaden Iceland Israel Ashkenazi Non-ashkenazi Italy* Campania Emilia Friuli Piedmont Puglia Sud Tyrol Veneto Veneto Japan Chiba

Years

~ 14,942

66.9t 1931-41

18

63,000

1.850,000 65.8t (zr= 0.419) 1,000,000 71.0t

* Estimates for other regions given in Nigro et al., (1983) [50] and DanielL (1984) [55]. t Prevalence in total male population. $ Prevalence in boys. n Ascertainment probability.

286 279

Lubs, (19741 [73] Kurland, (19581 [74] Stephens & Tyler, (195 I) [75] Morton & Chung, (19591 [2]

Zidar, (1990) [76] see also Faganel et al., (19771 [77]

A W o r l d Survey

21

Table 2. Duchenne muscular dystrophy: incidence in live male births (LMB) derived from various neonatal screening programmes Number Region Canada France Germany (voluntary) New Zealand United Kingdom Scotland

Affected

Total (LMB)

1986-87 1975-78 1977-84

5 12 48

18,000 71,091 176,600

278 169 272

Greenberg et al., (1988) [78] Dellamonica et al., (1983) [79] Scheuerbrandt et aL, (1986) [80]

1978

2

I 0,000

200

Drummond & Veale, (1978) [81], Drummond, (1979) [82]

1976-81

1

3356

298

Skinner et al., (1982 and unpublished) [83]

With a well defined disorder and in an exhaustive study of a clearly delineated population, rc will approach unity. Prevalence figures are especially valuable in planning for the medical, social and economic needs of the handicapped in the population. The term incidence is here used for the number of individuals born during a given period who will later develop the disease in relation to the number of live births over the same period. In the case of X-linked disorders the reference population would be the number of male live births, and for autosomal disorders the reference population would be the total number of live births. Again the probability of ascertainment may be taken into account [2, 6] where incidence (I): I

where

Incidence (x 10-~) Reference

Years

= A/rrN'

N' n,

= En,G,(1 - D,) = number in general population at age t G, = cumulative frequency of onset at age t among affecteds D, = cumulative frequency of death at age t among affecteds. Since many of these disorders are serious and lead to premature death the presumed incidence at birth would be expected to exceed the prevalence in the general population. However, the data are often too imprecise to always demonstrate such a difference, especially in the less severe conditions. DUCHENNE MUSCULAR DYSTROPHY

There have been many studies throughout the world of the prevalence and incidence of this Xlinked disorder (Tables 1 and 2). Despite increasing awareness of the disorder in more recent years, there has been no apparent increase in reported incidences, perhaps because any inflation in the past by the inclusion of other neuromuscular diseases has been counterbalanced in

more recent years by improved ascertainment of true cases [7]. In the more exhaustive and recent studies the incidence approaches 300 × 10 -6 or roughly 1 in 3500 male births. With regard to prevalence studies there is the added complication that the same reference population has not always been used by different investigators. Expressed in terms of the total male population, reported prevalence rates vary from 19.5-95.0 with a mean of around 63 x 10 -6. AUTOSOMAL RECESSIVE (DUCHENNE-LIKE) MUSCULAR DYSTROPHY OF CHILDHOOD

This appears to be a rare disorder in many countries with a prevalence of less than 5 × 10 -6 (Table 3). It is, however, commoner in certain Arabic communities in Tunisia [8] and the Sudan [9] and in Switzerland [10] and certain inbred communities in North America which originated from Switzerland [11-13]. In these populations differentiation from X-linked Duchenne muscular dystrophy could therefore present a problem. In other parts of the world it has been estimated that around 3-5% of isolated males diagnosed as having X-linked Duchenne muscular dystrophy may in fact have this clinically similar autosomal recessive disorder [7, 14]. BECKERMUSCULAR

DYSTROPHY

Until recently because of possible confusion with autosomal recessive limb girdle muscular dystrophy, the diagnosis of X-linked Becker muscular dystrophy could only be established with certainty when a proximal myopathy affected males in at least two generations of a family, the pattern of inheritance being consistent with that of an X-linked recessive trait. For this reason affected isolated males or brothers would usually not be included and ascertainment would therefore be incomplete. These data (Table 4) suggest that the incidence at birth could

A.E.H.

22

EMERY

Table 3. Autosomal recessive (Duchenne-like) muscular dystrophy of childhood: prevalence in the population and incidence at birth Prevalence Country

Year Affected

Germany Sudbaden Italy North East United Kingdom England (NE)

Total

Incidence × 10 "

Years

Affected

Total

1918 32

5

125,000

× I/) " Reference 40.0

Becker, ( 19801 [47]

1974

26

6.158,622

4.2

Danieli et al., (1974) [84]

1988

4

3,070,000

1.3

Gardner-Medwin & Sharpies, (19891 [68]

Table 4. Becker muscular dystrophy: prevalence in the male population and incidence in live male births (LMB) Prevalence Country

Year Affected

Total

Canada Alberta

1979

989,100 (total)

Finland Helsinki Germany Erfurt Italy Campania Veneto Norway Switzerland Yugoslavia Ljubljana

1980 1983

1990

17

44 4

12

3,335,577 293,833 (boys)

~ 1,000,000

Incidence × 10 "

Years

17.2

1950-74

7

420,374

16.7

1965 80

3

122,595

24.5

Lang et al.. 11989) [43]

1958 73

7

165,898

42.2

Spiegler & Herrmann, (19831 [46]

1960-66 1959-68

14 16

430,484 292,637

32.5 54.7

1921 41)

6

124,920

13.2 13.6

MUSCULAR

Monckton et al., 11982) [40]

Nigro et al., (1983) [50] Mostacciuolo et al., 119871 [57] Tangsrud & Halvorsen, 119881 [631 48.11 Moser et al., (1964) [66]

12.11

be about one-fifth of that for Duchenne muscular dystrophy and the prevalence in the male population around 14 x 10 6. However, Becket muscular dystrophy can now be clearly differentiated from limb girdle muscular dystrophy (as well as other clinically similar conditions) by using dystrophin assays, or e D N A probes [i 5]. It is therefore now possible to diagnose all cases of Becker muscular dystrophy, including non-familial cases, and so more precise figures for incidence and prevalence should become available in future. In fact a recent study conducted by Dr K. M. D. Bushby and Dr D. GardnerMedwin (personal communication, 1991) using molecular diagnostic methods in familial cases of Becker muscular dystrophy as well as in nonfamilial cases suspected of having this disease, has yielded a total prevalence of 24 x 10 6 in the general population, with an estimated birth incidence of 54 x 10 0. FACIOSCAPULOHUMERAL

Affected Tntal (LMB)x 10 ~ Reference

Zidar, ( 199111[761, see also Faganel et al., (19771 [77]

However, because many mildly affected cases often go undiagnosed, ascertainment is likely to be incomplete, even in the most thorough studies [16].

LIMB GIRDLE MUSCULAR

DYSTROPHY

The clinical features and nosological status of autosomal recessive limb girdle muscular dystrophy presenting in childhood or later in life have recently been critically reviewed [17]. Most published prevalence and incidence rates for mainly adult onset cases lie between 2 0 4 0 x 10 -6 (Table 6). But since it is now recognized that this disorder can be mimicked by a number of clinically similar neurogenic and myogenic conditions, particularly Becker muscular dystrophy in males and manifesting carriers of Duchenne muscular dystrophy in females [18], these data are artificially inflated. In one recent study [19] the prevalence of adult onset cases was at most 7 x 10 -6.

DYSTROPHY MYOTONIC

Published data give widely varying values for the prevalence and incidence of this autosomal dominant disorder from 2.2-66.9 x 10-" (Table 5). It is therefore difficult to give an overall figure which may lie between 10-20 x 10 -6.

DYSTROPHY

The reported prevalence rates in adults of this autosomal dominant disorder vary from 9.196.2 x 10 -6 (Table 7). An overall figure would appear [20] to be around 50 x 10 -6. However, in

23

A World Survey Table 5. Facioscapulohumeral muscular dystrophy: prevalence in the population and incidence at birth Prevalence Country

Year Affected

Canada Alberta Denmark Iceland Israel Italy North East Japan Kumamoto Shimane Libya Netherlands Norway

Incidence

Total

x 10 -6

1979 1965 1963 1973

31 -1 7

2,031,000 187,200 2,434,762

15.3 18.6 5.3 2.9

1974

38

6,158,622

6.2

1983 1975 1985 1982 1983

6 3 4 43 4

3.3 3.9 8.0 18.7 7.0

Poland Switzerland 1966 United K i n g d o m England (NE) 1955 Wales 1989 (Cardiff) 1989 U.S.A. Minnesota 1955 Wisconsin 1959

29 2

1,800,000 768,876 ~ 500,000 2,299,175 573,762 (children) -910,000

22 56 12

2,000,000 2,800,000 274,000

11.0 20.0 43.8)

2 2

29,885 3,700,000

66.9 2.3 (zr= 0.235)

36

1,996,377

18.0

Yugoslavia Ljubljana

1990

Years

Affected

Total

x 10 -6

12 -. .

828,880 -. .

14.5 26.0

1950-74 1965-75 . . . .

Reference Monckton et al., (1982) [40] Leth et al., (1985) [42] Gudmundsson, (1968) [48] Kott et al., (1973) [49] Danieli et al., (1974) [84]

I --

-

--

-

Araki et al., (1987) [59] Takeshita et aL, (1977) [32] Radhakrishnan et al., (1987) [61] Padberg, (1982) [16] Tangsrud & Halvorsen, (1988) [63] Prot, (1971) [64] Moser et al., (1966) [10]

4.0 2.2 -

-

22.7

r

-3.8

--

--

Walton, (1955) [67] Lunt et al., (1989) [85], Lunt, (1990) [86] Kurland, (1958) [74] Morton & Cbung, (1959) [2]

Zidar, (1990) [76], see also Faganel et al., (1977) [77]

Table 6. Limb girdle muscular dystrophy: prevalence in the population and incidence at birth Prevalence Country Canada Alberta Denmark Iceland Italy North East Japan Kumamoto Shimane Libya Norway Poland Switzerland United K i n g d o m England (NE) Scotland U.S.A. Wisconsin Yugoslavia Ljubljana

Incidence

Year

Affected

Total

× 10 -6

Years

1979 1965 1963

67 -7

2,031,000 -187,200

33.0 36.5 37.4

1974

117

6,158,622

19.0

1983 1975 1985 1983

28 22 19 2

15.6 28.6 37.0 3.5

---

1971 1966

46 36*

1,800,000 768,876 ~ 500,000 573,762 (children) 3,737,000 910,000

12.3 39.6

1946-57 --

1955 1979

20 5

2,000,000 750,728

10.0 6.7

1959

26

3,700,000

19.9 (Tr= 0.354)

1990

87

1,996,377

43.6

1950-74 1965-75 . .

.

Affected

Total

x 10 -6

23

828,880 -.

27.8 66.0

--

--

--

Danieli et aL, (1974) [841

---

-----

-----

Araki et aL, (1987) [59] Takeshita et al., (1977) [32] Radhakrishnan et al., (1987) [61] Tangsrud & Halvorsen, (1988) [63]

15

939,886

16.0

Prot, (1971) [64] Moser et al., (1966) [10]

.

.

.

.

--

--

--

--

--

65.3

Reference

Monckton et al., (1982) [40] Leth et al., (1985) [42] Gudmundsson, (1968) [48]

Walton, (1955) [67] Yates & Emery, (1985) [19] Morton & Chung, (1959) [21

Zidar (1990) [76], see also Faganel et al., (1977) [77]

* Adult onset in 10.

certain populations very much higher figures have been found due to founder effect and genetic isolation as in the case of Northern Quebec [20], Guam [21] and the northern Transvaal [22]. CONGENITAL

MYOTONIAS

There is considerable variation in the few reported studies so far. But for all forms taken together the prevalence would appear to approach 10 × 10 -6 (Table 8).

SPINAl, MUSCULAR

ATROPHIES

The childhood forms of proximal spinal muscular atrophy are the commonest forms of this group of diseases and in most cases are inherited as autosomal recessive traits. Data for the most severe type I (Werdnig-Hoffmann) disease, where affected children do not survive beyond the first few years of life, suggest that the birth incidence is around 40-60 x 1 0 - 6 (Table 9). However, this disorder is much commoner in

24

A. E. H. EMERY Table 7. Myotonic dystrophy: prevalence in the population and incidence at birth

Incidence

Prevalence Country

Year

U.S.A. Minnesota Yugoslavia Ljubljana

× 10 ~

Reference

828,880

44.6

Monckton et al.. 119821 [40] Grimm, ( 19751 [87] Gudmundsson, (I 968) [48]

Total

× 10 '

Years

Affected

114 ~3.000 18

2,031,000 ~55,000,000 187.200

56.1 -55.1) 96.2

1950 74

37

33

1,370.921

24. I

24

1,160,686

20.7

114 154

4,242.230 4,242,230

26.9 36.3

Mostacciuolo et al., (1987) [90] Mostacciuolo et al., (1987) [90]

36 7 7

1,800,001) 768,876 573,762 (children) 4,714,992

20.0 9.1 12.2

Araki et al., 119871 [59] Takeshita el al., 119771 [32] Tangsrud & Halvorsen (1988) [63] Klein (19581 [91] Todorov et al.. 11970) [92]

Canada Alberta 1979 Germany 1960 Iceland 1963 Ireland Northern 1951-56 [tal~ Turin 1979 Veneto 1975 severe cases all cases Japan Kumamoto 1983 Shimanc 1975 Norway 1983 Switzerland

Total

Affected

1945 56

229

48.6 78.0

Lynas, 11957) [88] 191[ 60

10

1960

346,546

279

5,5011,000

28.9

135.5" (Jr= I).374)

Pinessi et al., ( 19821 [89]

1955

I

29,885

33.5

Kurland. (1958) [74]

1990

52

1,996.377

26. I

Zidar, (199(I) [76] see uL~'o Faganel e l al,, (1977) [77]

*Refers to heterozygote frequency not actual affecteds.

Table 8. Congenital myotonias: prevalence in the population and incidence at birth

Incidence

Prevalence Country

Year

Germany Dominant 1960 myotonia Recessive 1960 myotonia Paramyotonia 1965 Iceland 1963 Italy Turin 1979 Switzerland 1945 56 U.S.A. Minnesota 1955 Yugoslavia Ljubljana 1990

Affected

Total

× 10 "

Years

Affected

Total

× 10 "

Reference

116

55,956,000

2. [

Becker, (1977) [93]

168

55,956,000

3.11

Becker, 11977) [93]

160 2

57,000,000 187,200

2.8 10.7

10 18

1,160,686 4,714,992

8.6 3.8

I

29,885

33.5

10

1,996,377

5.0

Becker, ( 19701 [94] Gudmundsson, 119681 [48] 1911 60

certain inbred communities such as the Egyptian Karaite in Israel [23], and Reunion Island, Madagascar [24]. The more benign (types II and III) forms o f the disease have a prevalence a m o n g children as high as 40 x 10 6 and around 12 x l0 6 in the general population.

HEREDITARY MOTOR AND SENSORY N EUROPATHIES

The hereditary motor and sensory neuropathies ( H M S N • Charcot-Marie-Tooth disease peroneal muscular atrophy) are a genetically

5

346,546

14.4

Pinessi et al., 11982) [89] Klein, 119581 [91] Kurland, 119581 [74]

Zidar ( 19901, [76] see al~so Faganel et al., (1977) [77]

heterogeneous group o f conditions which can now be subdivided on the basis o f clinical features and nerve conduction studies. But since a distinction has not always been made between the different forms, especially in earlier studies [25], prevalence data for all forms combined together are presented (Table 10). Because o f the considerable variation in reported prevalence rates (14-282 x 10 6) it is very difficult to give an overall figure, which appears to be around 100 x 10 -6 . However, Harding [26] believes that when all forms are combined together and ascertainment is complete, the total prevalence could approach 200 x l0 6.

A World Survey

25

Table 9. Spinal muscular atrophy: prevalence in the population and incidence at birth. Type I severe Werdnig-Hoffmann disease; type II intermediate; type III benign Kugelberg-Welander disease Prevalence Type

1+II + III

Country

Year Affected

Finland Hungary Norway

--1983

United Kingdom England -Canada 1962-64 Norway

Switzerland II + Ill Finland Norway United Kingdom England

Incidence

Total

× 10 -6

-1

573,762 (children)

-~20 24

573,762 (children)

--[ 983

-23

-573,762 (children)

1971

30

2,488,810

Affected

Total

55.7 66.1

Ignatius & Donner, (1989) [95] Czeizel & Hamula, (1989) [96] Tangsrud & Halvorsen, (1988) [63]

38.9 59.7

Pearn, (1973) [97] Winsor et al., (1971) [98]

-1.7

1971-85 1973-80 . .

53 91 .

952,228 1,376,928 .

-7.3

1966-71 1956-65

9 37

231,370 ~620,000

~2,748,500

1983

Years

41.8

x 10 6 Reference

--

Tangsrud & Halvorsen, (1988) [63]

--40.1

1960-69 1971-85

62 15 --

1,100,000 952,228

56.4 15.8 --

Zellweger & Hanhart, (1972) [99] Ignatius & Donner, (1989) [95] Tangsrud & Halvorsen, (1988) [63]

12.0

1960-69

15

365,166

41.1

Pearn, (1978) [100]

Table 10. Hereditary motor and sensory neuropathies: prevalence in the population Prevalence Country

Year

Affected

Finland Northern Southern Iceland Italy

1969-83 1989 1963

40

Veneto

1987

100"

1962-68 1967-68

Japan Ryukyuan Islands Norway Western Pacific

Total

× 10 ~

Reference

187,200

60 97 16

Rantala et al., (1986) [101] Kiuru, (1989) [102] Gudm undsson, (1969) [103]

1,067,130

94

Mostacciuolo et al., (1991) [104]

10

287,727

35

Kondo et al., (1970) [33]

106

725,000

146

Skre, (1974) [105]

1967

9

37,975

237

Chen et al., (1968) [21]

1985 1981

144 50

510,000 263,400 (children)

282 190

Combarros et al., (1987) [1061 Hagberg & Westerberg, (1983) [107]

1

46 117

71,101 750,000 2,500,000

14 61 47

Brewis et al., (1966) [28] Brooks & Emery, (1982) [108] Davis et al., (1978) [109]

1921-40

187

3,500,000

53

Herndon, (1954) [110]

1990

173

1,996,377

87

Zidar, (1990) [76] see also Faganel et al., (1977) [77]

Guam Spain Cantabria Sweden United Kingdom Carlisle Edinburgh

1961 1981

Newcastle

670,000

--

3

U.S.A. North Carolina Yugoslavia Lj ubljana

*Type I H M S N only.

FAMILIAL MOTOR

NEURONE

MYASTHENIA

DISEASE AND

(4 x 10- 6) of familial myasthenia gravis [31].

GRAVIS DISCUSSION

Prevalence studies of motor neurone disease (including amyotrophic lateral sclerosis) have been reviewed in detail [27] and most values range from 10-70 x 10 -6. The higher values of around 70 × 10 -6 may be the most reliable for many western countries [28, 29]. It has been estimated conservatively that around 5-10% of adult onset cases may be familial [30] and therefore the prevalence of these inherited cases would then be roughly 4-7 x 10 -6. This is comparable with the estimated prevalence

In considering the epidemiology of inherited neuromuscular diseases, considerable variations in prevalences and incidences are often evident in different studies. Sometimes these are a reflection of genetic differences in populations such as founder effect in certain dominant disorders, and inbreeding in the case of recessive disorders in genetically isolated populations. Some disorders may even be restricted to one population only as in the case of the Fukuyama type of congenital

26

A . E . H . EMERY

muscular dystrophy in Japan [32], the Ryukyuan type of spinal muscular atrophy in the islands of southern Japan [33], and the syndrome of muscle-eye-brain (MEB) disease in Finland [34]. The X-linked myopathy with excessive autophagy has also been reported only in Finland so far [35]. But variations in disease frequencies in different studies are more usually the result of different investigators having used different diagnostic criteria for a particular disorder and perhaps more especially to variations in the completeness of ascertaining cases in the population. The latter was a particularly important confounding factor in many earlier studies. Table 11. Estimated overall prevalences ( x 10 ") of the commoner inherited neuromuscular diseases in the general population. The figure for Becker muscular dystrophy is an underestimate and that for limb girdle muscular dystrophy an overestimate Muscular Dystrophies Duchenne Duchenne-like Becket Facioscapulohumeral Limb girdle Myotonic dystrophy Congenital myotonias Spinal muscular atrophies (II + Ill) Hereditary motor and sensory neuropathies Familial motor neurone disease and myasthenia gravis

32 5 > 7 20 < 40 50 I0

SUMMARY

A survey has been carried out of the world literature on the population prevalences and birth incidences of the more frequently inherited neuromuscular diseases, including the commoner forms of muscular dystrophy and spinal muscular atrophy, myotonic dystrophy, congenital myotonias, hereditary motor and sensory neuropathies, familial motor neurone disease and familial myasthenia gravis. Based on over 150 reported surveys it has been estimated that the total prevalence in the general population (excluding disorders which manifest only in infancy or early childhood) is around 286 x 10 ~' or that at least 1 in 3500 individuals may be expected to develop a disabling inherited neuromuscular disease at some time in childhood or later life. Acknowh, dgements I am most grateful to all those who very kindly provided epidemiological data from their own countries, to Drs David Gardner-Medwin and Jeffrey Sofaer for their helpful comments and advice in the preparation of this article, and to Mrs Isobel Black for her secretarial assistance.

12 REFERENCES 100 10 Total

286

For these various reasons, therefore, too much reliance should not be placed on the summary estimates given in the text. The figures do, however, allow a conservative estimate to be made of an overall prevalence among both sexes of 286 x 10 6(Table 11): that is, 1 in 3500of the population may be expected to have a disabling inherited neuromuscular disease presenting in childhood or in later life. This figure, however, excludes Werdnig-Hoffmann type I spinal muscular atrophy and the severe congenital forms of muscular dystrophy which are manifested only in infancy and early childhood, as well as disorders which can have serious consequences (such as malignant hyperthermia) but which are often asymptomatic. The congenital myopathies, mitochondrial myopathies and the rarer forms of muscular dystrophy and spinal muscular atrophy are also excluded because there are no reliable prevalence and incidence data. But if all these conditions were also included, the overall prevalence of disabling inherited neuromuscular diseases could well exceed 1 in 3000 of the population.

1. Myrianthopoulos N C. Neurogenetic directory, parts 1 and 2. In: Vinken P J, Bruyn G W, eds. Handbook q[ Clinical Neurology. Amsterdam: North-Holland, 1982, vols 42, 43. 2. Morton N E, Chung C S. Formal genetics of muscular dystrophy. Am J Hunt Genet 1959; 1!: 360-379. 3. Cavalli-Sforza L L, Bodmer W F. The Genetics o# Human Populations. San Francisco: W H Freeman 1971: 856-860. 4. Simpson S P. Estimating the ascertainment probability from the number of ascertainments per proband. Hum Hered 1983; 33:103 108. 5. Emery A E H. Methodology in Medical Genetics An Introduction to Statistical Methods, 2nd ed. Edinburgh: Churchill Livingstone, 1986: 39-40. 6. Yasuda N, Kondo K. No sex difference in mutation rates of Duchenne muscular dystrophy. J Med Genet 1980; |7: 106-111. 7. Emery A E H. Duehenne muscular dystrophy. Oxford: Oxford University Press, 1988. 8. Ben Hamida M, Fardeau M, Ania N. Severe childhood muscular dystrophy affecting both sexes and frequent in Tunisia. Muscle Nerve 1983; 6: 469-480. 9. Salih M A M, Omer M I A, Bayoumi R A, Karrar O, Johnson M. Severe autosomal recessive muscular dystrophy in an extended Sudanese kindred. Dev Med Child Neurol 1983; 25:43 52. 10. Moser H, Wiesmann U, Richterich R, Rossi E. Progressive Muskeldystrophie. VIII. H/iufigkeit, Klinik und Genetik der Typen I und II. Schweiz Med Woeh 1966; 96: 169-174, 205-211. 11. Jackson C E, Strehler D A. Limb-girdle muscular dystrophy: clinical manifestations and detection of preclinical disease. Pediatrics 1968; 41:495 502. 12. Shokeir M H K, Kobrinsky N L. Autosomal recessive muscular dystrophy in Manitoba Hutterites. Clin Genet 1976; 9: 197-202.

A World Survey 13. Shokeir M H K, Rozdilsky B. Muscular dystrophy in Saskatchewan Hutterites. Am J Med Genet 1985; 22: 487-493. 14. Zatz M, Passos-Bueno M R, Rapaport D. Estimate of the proportion of Duchenne muscular dystrophy with autosomal recessive inheritance. Am J Med Genet 1989; 32:407-4 10. 15. Norman A, Thomas N, Coakley J, Harper P. Distinction of Becker from limb-girdle muscular dystrophy by means of dystrophin cDNA probes. Lancet 1989; 1: 466-468. 16. Padberg G W A M. Facioscapulohumeral disease. Doctorate Dissertation. University of Leiden, 1982. 17. Rideau Y. Autosomal recessive muscular dystrophy. Acta Cardiomiol 1989; I: 109-140. 18. Walton J N, Gardner-Medwin D. The muscular dystrophies. In: Walton J N, ed. Disorders of Voluntary Muscle. Edinburgh: Churchill Livingstone, 1988: 519568. 19. Yates J R W, Emery A E H. A population study of adult onset limb-girdle muscular dystrophy. J Med Genet 1985; 22: 250-257. 20. Mathieu J, De Braekeleer M, Pr6vost C. Genealogical reconstruction of myotonic dystrophy in the SaguenayLac-Saint-Jean area (Quebec, Canada). Neurology 1990; 40: 839-842. 21. Chen K-M, Brody J A, Kurland L T. Patterns of neurologic diseases on Guam. Arch Neurol 1968; 19: 573-578. 22. Lotz B P, van der Meyden C H. Myotonic dystrophy. Part I. A genealogical study in the northern Transvaal. S Aft M e d J 1985; 67: 812-814. 23. Fried K, Mundel G. High incidence of spinal muscular atrophy type I (Werdnig-Hoffmann disease) in the Karaite community in Israel. Clin Genet 1977; 12: 250251. 24. Pascalet-Guidon M-J, Bois E, Feingold J, Mattei J-F, Combes J-C, Hamon C. Cluster of acute infantile spinal muscular atrophy (Werdnig-Hoffmann disease) in a limited area of Reunion Island. Clin Genet 1984; 26: 39-42. 25. Bobowick A R, Brody J A. Epidemiology of neurodegenerative system disorders. In: Vinken P J, Bruyn G W, eds. Handbook of Clinical Neurology. Amsterdam: North-Holland, 1975; Vol. 21: 3-42. 26. Harding A E. Personal communication, 1990. 27. Kurtzke J F. Epidemiology of amyotrophic lateral sclerosis. In: Rowland L P, ed. Human Motor Neuron Diseases. New York: Raven Press, 1982: 281-302. 28. Brewis M, Poskanzer D C, Rolland C, Miller H. Neurological disease in an English city. Acta Neurol Scand 1966; 42 (Suppl. 24): 19-23, 60-61. 29. Wade D T, Hewer R L. Epidemiology of some neurological diseases with special reference to work load on the NHS. Int Rehabil Med 1987; 8: 129-137. 30. Emery A E H, Holloway S. Familial motor neuron diseases. In: Rowland L P, ed. Human Motor Neuron Diseases. New York: Raven Press, 1982: 139-147. 31. Pirskanen R. Genetic aspects in myasthenia gravis. A family study of 264 Finnish patients. Acta Neurol Scand 1977; 56:365 388. 32. Takeshita K, Yoshino K, Kitahara T, Nakashima T, Kato N. Survey of Duchenne type and congenital type of muscular dystrophy in Shimane, Japan. Jap J Hum Genet 1977; 22: 43-47. 33. Kondo K, Tsubaki T, Sakamoto F. The Ryukyuan muscular atrophy. An obscure heritable neuromuscular disease found in the islands of Southern Japan. J Neurol Sci 1970; 11: 359-382. 34. Santavuori P, Somer H, Sainio K, Rapola J, Kruus S, Nikitin T, Ketonen L, Leisti J. Muscle-eye-brain disease (MEB). Brain Dev 1989; I1: 147-153. 35. Kalimo H, Savontaus M-L, Lang H, Palj~irvi L, Sonninen V, Dean P B, Katevuo K, Salminen A.

36.

37.

38. 39.

40. 41.

42.

43.

44.

27

X-linked myopathy with excessive autophagy: a new hereditary muscle disease. Ann Neurol 1988; 23: 258265. Cowan J, Macdessi J, Stark A, Morgan G. Incidence of Duchenne muscular dystrophy in New South Wales and the Australian Capital Territory. J Med Genet 1980; 17: 245-249. Lawrence E F, Brown B, Hopkins I J. Pseudohypertrophic muscular dystrophy of childhood: an epidemiological survey in Victoria. Aust N Z J Med 1973; 3: 142-151. Hurse P V, Kakulas B A. Genetic counselling in neuromuscular diseases in Western Australia. Proc Aust Assoc Neurol 1974; 11: 145-153. Kakulas B A, Hurse P V. The muscular dystrophies: results of carrier detection and genetic counselling in Western Australia. Rec Adelaide Children's Hosp 1977; 1: 232-243. Monckton G, Hoskin V, Warren S. Prevalence and incidence of muscular dystrophy in Alberta, Canada. Clin Genet 1982; 21: 19-24. Williams W R, Thompson M W, Morton N E. Complex segregation analysis and computer-assisted genetic risk assessment for Duchenne muscular dystrophy. Am J Med Genet 1983; 14: 315-333. Leth A, Wulff, K, Corfitsen M, Elmgreen J. Progressive muscular dystrophy in Denmark. Natural history, prevalence and incidence. Acta Paediatr Seand 1985; 74: 881-885. Lang H, Donner M, Ignatius J, et al. Epidemiology of muscular disorders in Finland (in Finnish). In: Lang H, ed. Lihastautien Kehittyvii Tutkimus Ja Hoito. Turku: Kiasma, 1989. Kunath B. Bericht fiber die Erfassung yon progressiven Muskeldystrophien im Bezirk Dresden. Proceedings of

a scientific meeting "Genetische Defekte", Neubrandenburg 14. 1983. 45. L6ssner J, Wagner A, eds. Beitriige zur klinischen Myologie. Leipzig: Hirzel, 1987.

46. Spiegler A W J, Herrmann F H. Erfassung und humangenetische Betreuung von Risikofamilien mit progressiver Muskeldystrophie der Typen Duchenne (DMD) und Becker-Kiener (BMD) im Bezirk Erfurt. Dt. Gesundh- Wesen 1983; 38: 994-1000. 47. Becker P E. Epidemiology of Duchenne muscular dystrophy in South-West Germany. In: Angelini C, Danieli G A, Fontanari D, eds. Muscular Dystrophy Research." Advances and New Trends. Amsterdam: Excerpta Medica, 1980: 149-156. 48. Gudmundsson K R. The prevalence of some neurological diseases in Iceland. Acta Neurol Scand 1968; 44: 57~9. 49. Kott E, Golan A, Don R, Bornstein B. Muscular dystrophy: the relative frequency in the different ethnic groups in Israel. Confin Neurol 1973; 35: 177-185. 50. Nigro G, Comi L I, Limongelli F M, et al. Prospective study of X-linked progressive muscular dystrophy in Campania. Muscle Nerve 1983; 6: 253-262. 51. Lucci B. Incidence, prevalence and mutation rate of Duchenne muscular dystrophy in the province of Reggio Emilia. In: Angelini C, Danieli G A, Fontanari D, eds. Muscular Dystrophy Research." Advances and New Trends. Amsterdam: Excerpta Medica, 1980: 289290. 52. Nigris P. Personal communication to G A Danieli, 1984. 53. Schiffer D, Bertolotto A, De Marchi M, et al. Epidemiology of Duchenne muscular dystrophy in the province of Turin. ltal J Neurol Sci 1981; 2:81-84. 54. Ferrari E, Intino M T, Perniola T, Russo M G. Epidemiology of Duchenne dystrophy and carrier detection in Puglia. Preliminary reports. In: Angelini C, Danieli G A, Fontanari D, eds. Muscular Dystrophy

28

A . E . H . EMERY

Research." Advances and New Trends. Amsterdam: Excepta Medica, 1980:264 265. 55. Danieli G A. Studies on the prevalence of the Duchenne muscular dystrophy genotype at birth. In: ten Kate L P, Pearson P L, Stadhouders A M, eds. Research into the Origin and Treatment o f Muscular Dystrophy. Amsterdam: Excerpta Medica, 1984:17 32. 56. Danieli G A, Mostacciuolo M L, Bonfante A, Angelini C. Duchenne muscular dystrophy: a population study. Hum Genet 1977; 35:225 231. 57. Mostacciuolo M L, Lombardi A, Cambissa V, Danieli G A, Angelini C. Population data on benign and severe forms of X-linked muscular dystrophy, Hum Genet 1987; 75: 217-220. 58. Kuroiwa Y, Miyazaki T. Epidemiological study of myopathy in Japan. In: Milhorat A T, ed. Explorato O, Concepts in Muscular Dystrophy and Related Disorders. Amsterdam: Excerpta Medica, 1967: lnt Congr Ser 147: 98-102. 59. Araki S, Uchino M, Kumamoto T. Prevalence studies of multiple sclerosis, myasthenia gravis, and myopathies in Kumamoto District, Japan. Neuroepidemiology 1987; 6: 120-129. 60. Kanamori M, Morton N E, Fujiki K, Kondo K. Genetic epidemiology of Duchenne muscular dystrophy in Japan: classical segregation analysis. Gen Epidemiol 1987; 4: 425-432. 61. Radhakrishnan K, EI-Mangoush M A, Gerryo S E. Descriptive epidemiology of selected neuromuscular disorders in Benghazi, Libya. Acta Neurol Stand 1987; 75:95 100. 62. van Essen A J, ten Kate L P. Epidemiologic survey of Duchenne muscular dystrophy in The Netherlands. Preliminary results. In: ten Kate L P, Pearson P L, Stadhouders A M, eds. Research into the Or~in and Treatment of Muscular Dystrophy. Amsterdam: Excerpta Medica, 1984: 33-40. 63. 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. 64. Prot J. Genetic-epidemiological studies in progressive muscular dystrophy. J Med Genet 197"t; 8: 90-96. 65. Radu H, Sark6zi A. Personal communication to P Becker. see Becker 1980. 66. Moser H, Wiesmann U, Richterich R, Rossi E. Progressive Muskeldystrophie. VI. Haufigkeit, Klinik und Genetik der Duchenne-Form. Schweiz Med Woch 1964; 94: 1610-1621. 67. Walton J N. On the inheritance of muscular dystrophy. Ann Hum Genet 1955; 20: 1-38. 68. Gardner-Medwin D, Sharpies P. Some studies of the Duchenne and autosomal recessive types of muscular dystrophy. Brain Dev 1989; ll: 91 97. 69. Blyth H, Pugh R J. Muscular dystrophy in childhood. The genetic aspect. Ann Hum Genet 1959; 23:127 163. 70. Bundey S. A genetic study of Duchenne muscular dystrophy in the West Midlands. J Med Genet 1981 : 18: 1-7. 71. Stevenson A C. Muscular dystrophy in Northern Ireland. IV. Some additional data. Ann Hum Genet 1958; 22: 231-234. 72. Brooks A P, Emery A E H. The incidence of Duchenne muscular dystrophy in the South East of Scotland. Clin Genet 1977; 11: 29~294. 73. Lubs M L. Hemophilia A and Duchenne muscular dystrophy in Colorado. Am J Hum Genet 1974; 26: 56A (Abstr.). 74. Kurland L T. Descriptive epidemiology of selected neurologic and myopathic disorders with particular reference to a survey in Rochester, Minnesota. J Chron Dis 1958; 8: 378-418.

75. Stephens F E, Tyler F H. Studies in disorders of muscle. V. The inheritance of childhood progressive muscular dystrophy in 33 kindreds. Am J Hum Genet 1951; 3: 111-125. 76. Zidar J. Report of the number of neuromuscular patients registered at the Neuromuscular Unit in Ljubljana, Yugoslavia. Personal communication, 1990. 77. Faganel J, Lavri~ A, Srgen V, Tivadar 1. Degenerativne ~iv~ano-mi~i~ne bolesti u Sloveniji. Neurologija 1977; 25:29-33 (in Yugoslavian). 78. Greenberg C R, Rohringer M, Jacobs H K, Averill N, Nylen E, van Ommen G J B, Wrogemann K. Gene studies in newborn males with Duchenne muscular dystrophy detected by neonatal screening. Lancet 1988; 2: 425-427. 79. Dellamonica C, Collombel C, Cotte J, Addis P. Screening for neonatal Duchenne muscular dystrophy by bioluminescencemeasurement ofcreatine kinase in a blood sample spotted on paper. Clin Chem 1983; 29: 161-163. 80. Scheuerbrandt G, Lundin A, L6vgren T, Mortier W. Screening for Duchenne muscular dystrophy: an improved screening test for creatine kinase and its application in an infant screening program. Muscle Nerve 1986; 9:11-23. 81. Drummond L M, Veale A M O. Muscular dystrophy screening. Lancet 1978; i: 1258-1259. 82. Drummond L M. Creatine phosphokinase levels in the newborn and their use in screening for Duchenne muscular dystrophy. Arch Dis Child 1979; 54: 362-366. 83. Skinner R, Emery A E H, Scheuerbrandt G, Syme J. Feasibility of neonatal screening for Duchenne muscular dystrophy. J M e d Genet 1982; 19: 1-3. 84. Danieli G A, Vecchi C, Angelini C. Geographic distribution of hereditary myopathies in Northeast Italy. SocialBio11974; 21:235 241. 85. Lunt P W, Compston D A S, Harper P S. Estimation of age dependent penetrance in facioscapulohumeral muscular dystrophy by minimising ascertainment bias. J Med Genet 1989; 26:755 760. 86. Lunt P. Facioscapulohumeral muscular dystrophy. MD Thesis, 1990. 87. Grimm T. the age of onset and the age of death in patients with dystrophia myotonica. J Gbnbt Hum 1975; 23:301-308. 88. Lynas M A. Dystrophia myotonica with special reference to Northern Ireland. Ann Hum Genet 1957; 21: 318-351. 89. Pinessi L, Bergamini L, Cantelto R, Di Tizio C. Myotonia congenita and myotonic dystrophy: descriptive epidemiological investigation in Turin, Italy (1955-.1979). I t a l J N e u r o l Sci 1982; 3: 207-210. 90. Mostacciuolo M L, Barbujani G, Armani M, Danieli G A, Angelini C. Genetic epidemiology of myotonic dystrophy. Genet Epidemio11987; 4: 289-298. 91. Klein D. La dystrophic myotonique (Steinert) et la myotonie cong6nitale (Thomsen) en Suisse. J Gknkt Hum (Suppl.) 1958; 7: 1-328. 92. Todorov A, J6quier M, Klein D, Morton N E. Analyse de la s6gr6gation dans la dystrophie myotonique. J Gknkt Hum 1970; 18: 387-406. 93. Becker P E. Myotonia Congenita and Syndromes Associated with Myotonia. Stuttgart: Georg Thieme, 1977. 94. Becker P E. Paramyotonia Congenita (Euh, nberg). Stuttgart: Georg Thieme, 1970. 95. Ignatius J, Donner M. Epidemiology of childhood spinal muscular atrophy (in Finnish). In: Lang H, ed. Lihastautien Kehittyvii Tutkimus Ja Hoito. Turku: Kiasma, 1989. 96. Czeizel A, Hamula J. A Hungarian study on Werdnig- Hoffmann disease. J Med Genet 1989; 26: 761 763.

A World Survey 97. Pearn J H. The gene frequency of acute WerdnigHoffmann disease (SMA Type I). A total population survey in North-East England. J Med Genet 1973; 10: 260-265. 98. 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. 99. Zellweger H, Hanhart E. The infantile proximal spinal muscular atrophies in Switzerland. Heir Paediat Acta 1972; 27: 355-360. 100. Pearn J. Incidence, prevalence, and gene frequency studies of chronic childhood spinal muscular atrophy. J Med Genet 1978; 15: 409-413. 101. Rantala H, Tolonen U, Myllyla V. Charcot-MarieTooth disease in Northern Finland. Ann Clin Res 1986; 18: 154-159. 102. Kiuru A. Genetic and epidemiological findings concerning the Charcot-Marie-Tooth syndrome in Finland (in Finnish). In: Lang H, ed. Lihastautien Kehittyvii Tutkimus Ja Hoito. Turku: Kiasma, 1989. 103. Gudmundsson K R, Prevalence and occurrence of some

104. 105. 106. 107. 108. 109.

110.

29

rare neurological diseases in Iceland. Acta Neurol Scand 1969; 45:114-118. Mostacciuolo M L, Micaglio G, Fardin P, Danieli G A. Genetic epidemiology of hereditary motor sensory neuropathies (type I). Am J Med Genet 1991 (in press). Skre H. Genetic and clinical aspects of Charcot-MarieTooth's disease. Clin Genet 1974; 6:98-118. Combarros O, Calleja J, Polo J M, Berciano J. Prevalence of hereditary motor and sensory neuropathy in Cantabria. Aeta Neurol Scand 1987; 75: 9-12. Hagberg B, Westerberg B. Hereditary motor and sensory neuropathies in Swedish children. Acta Paediatr Scand 1983; 72: 379-383. Brooks A P, Emery A E H. A family study of CharcotMarie-Tooth disease. J Med Genet 1982; 19: 88-93. Davis C J F, Bradley W G, Madrid R. The peroneal muscular atrophy syndrome. 1. Clinical, genetic and electrophysiological findings and classification. J Gknkt Hum 1978; 26:311-349. Herndon C N. Three North Carolina surveys. Am J Hum Genet 1954; 6: 65-74.