Background
SMA type | OMIM number | Age of onset | Highest achieved motor function | Natural age of death |
---|---|---|---|---|
0 | - | Prenatal/ Foetal | Nil | <6 months |
I | 253300 | <6 months | Sit with support only | <2 years |
II | 253550 | 6–18 months | Sit independently | >2 years |
III | 253400 | >18 months | Stand and walk | Adulthood |
IV | 271150 | Adult (2nd or 3rd decade) | Walk during adulthood | Adult |
Methods
Prevalence and incidence of SMA
Prevalence
Country | Time point | SMA | Type I | Quality and comparability | Reference | |||||||
No of patients | Population | per 100,000 | No of patients | Population | per 100,000 | |||||||
Norway (Southern + Eastern) | 01/01/1983 | 24 | 573,762 | 4.18 | 1 | 573,762 | 0.17 | Only included patients below 18 years of age | Tangsrud_1988 [25] | |||
Sweden (Western) | 31/12/2006 | 11 | 340,179 | 3.23 | - | - | - | Genetic diagnosis used Only included patients below 16 years of age | Arkblad_2009 [23] | |||
Sweden (Western) | 01/01/1995 | 10 | 359,676 | 2.78 | 1 | 359,676 | 0.28 | Only included patients below 16 years of age | Darin_2000 [24] | |||
Estonia | 31/12/2003 | - | - | - | 2 | 1,351,069 | 0.15 | Genetic diagnosis used | Vaidla_2006 [34] | |||
United Kingdom (Northern Ireland) | 30/06/1994 | 22 | 1,573,282 | 1.40 | - | - | - | Hughes_1996 [110] | ||||
United Kingdom (Northern England) | 01/08/2007 | 56 | 2,991,517 | 1.87 | 3 | 2,991,517 | 0.10 | Genetic diagnosis used in most cases | Norwood_2009 [32] | |||
Germany (West‑Thüringen) | 31/12/1987 | - | - | - | 3 | 1,778,200 | 0.17 | Thieme_1993 [33] | ||||
Italy (Bologna) | 31/12/1989 | 10 | 152,529 | 6.56 | - | - | - | Only included patients below 20 years of age | Merlini_1992 [22] | |||
Saudi Arabia (Northeast, Thugbah) | 02/08/1989 | 3 | 22,630 | 13.26 | 1 | 22,630 | 4.42 | In half of the cases parental consanguinity was observed | al Rajeh_1993 [29] | |||
China (Hongkong) | 30/06/2001 | 25 | 1,335,469 | 1.87 | 2 | 1,335,469 | 0.15 | Partly used genetic diagnosis | Chung_2003 [31] | |||
Canada (Toronto) | 1962–1964 | 20.33 | 2,748,500 | 0.74 | - | - | - | Average of a three-year period | Winsor_1971 [111] | |||
Country | Time point | Type II | Type III | Type II + III | Quality and comparability | Reference | ||||||
No of patients | Population | per 100,000 | No of patients | Population | per 100,000 | No of patients | Population | per 100,000 | ||||
Norway (Southern + Eastern) | 01/01/1983 | 21 | 573,762 | 3.66 | 2 | 573,762 | 0.35 | 23 | 573,762 | 4.01 | Only included patients below 18 years of age | Tangsrud_1988 [25] |
Sweden (Western) | 01/01/1995 | 4 | 359,676 | 1.11 | 5 | 359,676 | 1.39 | 9 | 359,676 | 2.50 | Only included patients below 16 years of age | Darin_2000 [24] |
United Kingdom (Northern England) | 01/08/2007 | 17 | 2,991,517 | 0.57 | 36 | 2,991,517 | 1.20 | 53 | 2,991,517 | 1.77 | Genetic diagnosis used in most casesa
| Norwood_2009 [32] |
United Kingdom (Northeast England) | June 1971 | - | - | - | - | - | - | 30 | 2,488,810 | 1.21 | Type II/III patients defined as: onset of disease between birth and 8 years of age, survival above 18 months of age | Pearn_1978 [41] |
Germany (West‑Thüringen) | 31/12/1980 | - | - | - | - | - | - | 29 | 1,785,239 | 1.62 | Type II/III patients defined as: survival above 4 years of age Exact number of patients not mentionedb
| Thieme_1994 [43] |
Poland (Warsaw) | 31/12/1985 | - | - | - | - | - | - | 21 | 1,659,385 | 1.26 | Exact number of patients not mentionedb
| Spiegler_1990 [42] |
Libya (Benghazi) | 31/12/1986 | - | - | - | - | - | - | 12 | - | 2.30 | In half of the cases parental consanguinity was observed | Radhakrishan_1988 [48] |
Saudi Arabia (Northeast, Thugbah) | 02/08/1989 | 2 | 22,630 | 8.84 | - | - | - | - | - | - | In half of the cases parental consanguinity was observed | al Rajeh_1993 [29] |
China (Hongkong) | 30/06/2001 | 9 | 1,335,469 | 0.67 | 14 | 1,335,469 | 1.05 | 23 | 1,335,469 | 1.72 | Partly used genetic diagnosis | Chung_2003 [31] |
Prevalence by SMA subtype
Incidence
Country | Timeframe | SMA | Type I | Quality and comparability | Reference | |||||||
No of patients | Population | per 100,000 | No of patients | Population | per 100,000 | |||||||
Iceland | 1982–1996 | 9 | 65,584 | 13.7 | 4 | 65,584 | 6.1 | Ludvigsson_1999 [112] | ||||
Sweden (Western) | 1980–2006 | 45 | 531,746 | 8.5 | 19 | 531,746 | 3.6 | Genetic diagnosis used Only included patients below 16 years of age | Arkblad_2009 [23] | |||
Sweden (Western) | 1979–1994 | 21 | 343,941 | 6.1 | 13 | 343,941 | 3.8 | Only included patients below 16 years of age | Darin_2000 [24] | |||
Finland | 1971–1985 | 68 | 952,228 | 7.1 | 53 | 952,228 | 5.6 | Ignatius_1989 [51] | ||||
Estonia | 1994–2003 | 15 | 129,832 | 11.6 | 9 | 129,832 | 6.9 | Genetic diagnosis used | Vaidla_2006 [34] | |||
United Kingdom (South Wales) | 1973–1989 | - | - | - | - | - | 4.4 | No details provided | MacMillan_1991 [113] | |||
United Kingdom (Northeast England) | 1966–1971 | - | - | - | 9 | 231,370 | 3.9 | Type I defined as onset of disease before 12 months of age | Pearn_1973 [52] | |||
Germany (West-Thüringen) | 1974–1987 | - | - | - | 33 | 336,663 | 9.8 | Thieme_1993 [33] | ||||
Switzerland | 1960–1969 | - | - | - | 62 | 1,100,000 | 5.6 | Probably also contains some type II patients | Zellweger_1972 [55] | |||
Poland (Warsaw) | 1976–1985 | 22 | 214,217 | 10.3 | 11 | 214,217 | 5.1 | Patients described as type Ib reclassified as type II according to the description | Spiegler_1990 [42] | |||
Poland | 1998–2005 | 304 | 2,963,783 | 10.3 | 209 | 2,963,783 | 7.1 | Genetic diagnosis used | Jedrzejowska_2010 [73] | |||
Slovakia | - | - | 17.8 | - | - | 8.1 | Kvasnicova_1994 [44] | |||||
Hungary | 1973–1980 | - | - | - | 91 | 1,376,928 | 6.6 | Czeizel_1989 [50] | ||||
Italy (Northeast) | 1960–1983 | 67 | 859,891 | 7.8 | 35 | 859,891 | 4.1 | Mostacciuolo_1992 [114] | ||||
Italy (Bologna) | 1970–1989 | 17 | 150,978 | 11.3 | 8 | 150,978 | 5.3 | Only included patients below 20 years of age | Merlini_1992 [22] | |||
Libya (Benghazi) | 1983–1986 | 18 | 75,000 | 24 | 6 | 75,000 | 8 | In half of the cases parental consanguinity was observed Population number is an estimation | Radhakrishan_1988 [48] | |||
Reunion Island | 1969–1980 | - | - | - | 19 | 24,000 | 79 | In 13 siblings of a European community Population number is an estimation | Pascalet-Guideon_1984 [115] | |||
Israel | 1970–1975 | - | - | - | 4 | 1600 | 250 | In an Egyptian Karaite community Population number is an estimation | Fried_1977 [116] | |||
Canada (Toronto) | 1955–1965 | 37 | 617,520 | 6.0 | - | - | - | Winsor_1971 [111] | ||||
USA (Ohio) | 4 | 40,103 | 10.0 | - | - | - | Genetic diagnosis used | Prior_2010 [101] | ||||
USA (North Dakota) | 1980–1987 | - | - | - | 14 | 94,092 | 14.9 | Burd_1991 [53] | ||||
Cuba | 1996–2002 | 51 | 1,018,454 | 5.0 | 36 | 1,018,454 | 3.5 | Partly used genetic diagnosis | Zaldivar_2002 [45] | |||
Country | Timeframe | Type II | Type III | Type II + III | Quality and comparability | Reference | ||||||
No of patients | Population | per 100,000 | No of patients | Population | per 100,000 | No of patients | Population | per 100,000 | ||||
Iceland | 1982–1996 | 2 | 65,584 | 3.0 | 3 | 65,584 | 4.6 | 5 | 65,584 | 7.6 | Ludvigsson_1999 [112] | |
Sweden (Western) | 1980–2006 | 11 | 531,746 | 2.1 | 15 | 531,746 | 2.8 | 26 | 531,746 | 4.9 | Genetic diagnosis used Only included patients below 16 years of age | Arkblad_2009 [23] |
Sweden (Western) | 1979–1994 | 3 | 343,941 | 0.9b
| 5 | 343,941 | 1.5 | 8 | 343,941 | 2.3 | Only included patients below 16 years of age | Darin_2000 [24] |
Finland | 1971–1985 | - | - | - | - | - | - | 15 | 952,228 | 1.6 | Ignatius_1989 [51] | |
United Kingdom (Northeast England) | 1960–1969 | - | - | - | - | - | - | 15k
| 365,166 | 4.1 | Pearn_1978 [41] | |
Germany (West-Thüringen) | 1965–1980 | - | - | - | - | - | - | 42 | 395,646 | 10.6 | Type II/III patients defined as: survival above 4 years of age | Thieme_1994 [43] |
Poland (Warsaw) | 1976–1985 | 10 | 214,217 | 4.7 | 1 | 214,217 | 0.5 | 11 | 214,217 | 5.1 | Type II defined as onset of disease before 12 months of age | Spiegler_1990 [42] |
Poland | 1998–2005 | 37 | 2,963,783 | 1.2 | 58 | 2,963,783 | 2.0 | 95 | 2,963,783 | 3.2 | Genetic diagnosis used | Jedrzejowska_2010 [73] |
Slovakia | - | - | 3.7 | - | - | 5.9 | - | - | 9.6 | Kvasnicova_1994 [44] | ||
Italy (Northeast) | 1960–1983 | 19 | 859,891 | 2.2 | 13 | 859,891 | 1.5 | 32 | 859,891 | 3.7 | Mostacciuolo_1992 [114] | |
Italy (Bologna) | 1970–1989 | 8 | 150,978 | 5.3f
| 1 | 150,978 | 0.7 | 9 | 150,978 | 6.0 | Only included patients below 20 years of age | Merlini_1992 [22] |
Libya (Benghazi) | 1983–1986 | - | - | - | - | - | - | 12 | 75,000 | 16 | In half of the cases parental consanguinity was observed Population number is an estimation | Radhakrishan_1988 [48] |
Incidence by subtype
Considerations for comparing studies
Carrier frequency in SMA
Subpopulation differences
Population | Number of identified carriers | Number of study participants | Carrier frequency | 95% CI |
---|---|---|---|---|
Araba
| 152 | 9058 | 0.017 | 0.014–0.019 |
Asian | 2492 | 119,718 | 0.021 | 0.020–0.022 |
Asian Indian | 20 | 1465 | 0.014 | 0.008–0.020 |
Black (Sub-Saharan ancestry) | 80 | 8012 | 0.010 | 0.008–0.012 |
Caucasian | 680 | 31,549 | 0.022 | 0.020–0.023 |
Hispanic | 127 | 9649 | 0.013 | 0.011–0.015 |
Jewish | 1059 | 59,196 | 0.018 | 0.017–0.019 |
SMN1 copy number differences between populations
Frequency by number of SMN1 copies on a single allele | ||||||
---|---|---|---|---|---|---|
0 Copies | 1 Copy | 2 Copies | ||||
Ethnicitya
| Portion | 95% CI | Portion | 95% CI | Portion | 95% CI |
Asian | 0.010 | 0.010–0.011 | 0.949 | 0.948–0.950 | 0.040 | 0.039–0.041 |
Asian Indianb
| 0.010 | 0.006–0.015 | 0.908 | 0.894–0.921 | 0.082 | 0.070–0.095 |
Black (Sub-Saharan ancestry) | 0.007 | 0.005–0.009 | 0.717 | 0.708–0.725 | 0.276 | 0.268–0.285 |
Caucasian | 0.011 | 0.010–0.012 | 0.954 | 0.952–0.955 | 0.035 | 0.034–0.037 |
Hispanic | 0.007 | 0.006–0.008 | 0.915 | 0.911–0.919 | 0.078 | 0.074–0.082 |
Jewish | 0.010 | 0.009–0.011 | 0.934 | 0.931–0.936 | 0.057 | 0.054–0.059 |
Adjusted carrier and disease frequencies | ||||||
---|---|---|---|---|---|---|
1 SMN1 copy carriers | 2 SMN1 copies carriers | Disease Frequency | ||||
Ethnicity | Frequency | 95% CI | Frequency | 95% CI | Frequency | 95% CI |
Asian | 0.022 | 0.021–0.023 | 0.0014 | 0.0012–0.0015 | 1.3E-04 | 1.2E-04-1.4E-04 |
Asian Indiana
| 0.020 | 0.012–0.030 | 0.0021 | 0.0014–0.0030 | 1.0E-04 | 4.0E-05-2.4E-04 |
Black (Sub-Saharan ancestry) | 0.014 | 0.011–0.018 | 0.0042 | 0.0034–0.0052 | 5.3E-05 | 3.4E-05-8.1E-05 |
Caucasian | 0.022 | 0.021–0.024 | 0.0013 | 0.0011–0.0014 | 1.3E-04 | 1.1E-04-1.5E-04 |
Hispanic | 0.014 | 0.011–0.017 | 0.0015 | 0.0013–0.0018 | 5.0E-05 | 3.5E-05-7.0E-05 |
Jewish | 0.020 | 0.018–0.022 | 0.0016 | 0.0014–0.0018 | 1.0E-04 | 8.3E-05-1.2E-04 |
Ethnicity | Incidence estimate (1 in) | 95% CI |
---|---|---|
Asian | 8009 | 7382–8684 |
Asian Indiana
| 9655 | 4227–25,057 |
Black (Sub-Saharan ancestry) | 18,808 | 12,331–29,559 |
Caucasian | 7829 | 6750–9093 |
Hispanic | 20,134 | 14,218–28,894 |
Jewish | 10,000 | 8343–12,038 |