Table 1: Familial ALS - known inheritance patterns

Inheritance Pattern	Chromosomal linkage	Unique features	Reference
Autosomal Dominant
ALS 1	21q22.1	Cu/Zn superoxide dismutase mutations	55
ALS X	Xp11 - q12	Adult onset	206
ALS 3		Adult onset; absence of linkage to Cu/Zn superoxide dismutase	207
ALS 4	9q34	Juvenile onset, complete penetrance; very slow progression; distal limb amyotrophy with pyramidal signs	208,209
ALS 6	9q21 - q22	Frontotemporal dementia associated	53
ALS with bulbar onset	unknown	Japanese family; juvenile onset with prominent early onset bulbar dysfunction; slow progression; dementia	210
NFH	22q12.1 - q22	Mutations in KSP repeats (not observed in fALS; only found in sporadic ALS)	115-118
Autosomal recessive
ALS 2	2q33 - q35	Spastic pseudobulbar syndrome with spastic paraplegia; childhood onset; slow progression,	2,211
ALS 5	15q15.1 - q21.1	Not pseudobulbar; distal amyotrophy; minor spasticity; long-term survival	212
Brown-Vialetto-van Laere syndrome		Progressive bulbar paralysis; childhood onset; progressive deafness; pyramidal signs;	213
X-linked
Kennedy’s syndrome	Xq12	Progressive muscle atrophy; gynecomastia; reduced fertility; Androgen receptor gene mutation (trinucleotide (CAG) repeat)	214-217
Miscellaneous
Hexosaminidase A and B	15q23 - q24	Late onset GM2 gangliosidosis	218-221
Disinhibition-dementia-parkinsonism-amyotrophy syndrome	Chr 17	Allelic with frontotemporal dementia and parkinsonism	54

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Table 2: Familial ALS 1 - general syndrome features associated with specific point mutations

Lower motor neuron predominant	A4V; L84V; D101N
Slow progression	G37R (18y); G41D (11y); G93C; L144S; L144F
Rapid progression	A4T (1.5y); N86S (homozygous, 5 months); L106V (1.2y); V148G (2y)
Late onset	G85R; H46R
Early onset	G37R; L38V
Female predominant	G41D
Bulbar onset	V148I
Low penetrance	D90A; I113T

(modified in part from Andersen PM, Morita M, Brown RH, Jr. Genetics of amyotrophic lateral sclerosis: an overview. In: Brown RH, Jr., Meininger V, Swash M, eds. Amyotrophic lateral sclerosis. London: Martin Dunitz Ltd., 2000: 223-250. )

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