Table S2 – Detailed list of 51 neuromuscular disorders (16 mapped and 28 with a cloned gene) characterized by neurological symptoms such as
epilepsy, spastic paraplegia, ataxia, etc. Entries are listed in alphabetical order but those that have an OMIM number are indicated
first, followed by those that have appeared only in PubMed publications. All entries indicated in red are allelic to the most common or
first described condition, i.e. due to mutations in the same gene (e.g. spastic paraplegia 2 and Baar-Gabriel are due to mutations in the
PLP1 gene, just like the Pelizaeus-Merzbacher disease). If a condition was not mapped by linkage analysis but through a cytogenetic
abnormality (translocation, microdeletion, duplication), this fact has been indicated in the notes column.
OMIM
/Ref.
Name
Locus
Gene
Notes
Description
1
2
#300100
#300578
Adrenoleukodystrophy
Xq28
Aldred - Xp11.3 deletion Xp11.3
syndrome
ABCD1 *300371
microdeletion
(see description)
enzyme deficiency
Spastic quadriparesis, impaired vision, ataxia, dementia
Retinitis pigmentosa, microcephaly
microdeletion including RP2 (*312600), SLC9A7 (*300368), CHST7
(*300375), ZNF674 (+300573) and ZNF673 (*300585) genes, and 2
genes encoding microRNAs (MIRN221, *300568; MIRN222, *300569).
learning disabilities, retinal dystrophy, and short stature
Severe hypotonia, joint contractures, spastic paraplegia, severe
muscular atrophy, nistagmus, high serum T3 and FT3
spastic tetraparesis, slowly progressive
Early death, hypotonia, ataxia, deafness, loss of vision, recurrent
infections
Pseudobulbar palsy with dysarthria and oropharyngoglossal
dysfunction, epilepsy with atonic and tonic-clonic seizures,
polymicrogyria with simplified 4-layered or unlayered cortex
(Spino)cerebellar ataxia, nystagmus, dysarthria, mild MR or learning
disability
nonspecific MR (MRX60)
Motor-sensory neuropathy, formerly listed as Ionasescu (Family 1)
3
#300578
#300523
Lugtenberg
Allan-Herndon-Dudley
Xq13.2
SLC16A2 / MCT8
*300095
4
309640
#301835
Davis
Arts
Xq22.3
PRPS1 *311850
5
%300388
Bilat. Perisylvian
Polymicrogyria
Xq28
SRPX2 *300642
6
#300486
Cerebellar ataxia
Xq12
OPHN1 *300127
7
%302801
8
%310490
9
#300352
10
11
#300257
(309660)
#310200
12
%300088
MRX
CMTX2 / Charcot-MarieTooth X-linked 2
CMTX4 / CowchockFishbeck
Creatine transporter
deficiency
Danon disease
Bergia
Duchenne muscular
dystrophy
EFMR
13
14
309560
#300491
Fitzsimmons
Garcia
Xp22
Xq24q26.1
Xq28
Motor-sensory neuropathy and deafness
SLC6A8 *300036
Xq24
LAMP2 *309060
Xp21.1-2
DMD *300377
Xq21.3q22.2
Xp11.23
Seizures, midface hypoplasia, unfolded helices, stub thumbs,
hyperextensible joints [K8085]
vacuolar hypertrophic cardiomyopathy, proximal muscle weakness
Cardiomyopathy (lethal), scapuloperoneal muscular dystrophy, myopia
Pseudohypertrofic muscular dystrophy
dominant, males
spared
SYN1 *313440
Mental retardation and epilepsy in females only, males spared
Spastic paraplegia, pes cavus, palmoplantar hyperkeratosis
Epilepsy, learning difficulties, macrocephaly, and aggressive behavior
15
*305915
GRIA3 inactivation
see ref.[1]
%309555 Gustavson
Xq25
#307000
#303350
#303350
Xq28
19
20
HSAS
MASA
Spastic paraplegia 1 /
SPG1
#304100
Agenesis of Corpus
Callosum, partial
#300607
Hyperekplexia and
see ref.[2] epilepsy
#300322
Lesch-Nyhan
#300067
LISX / SCLH
21
22
+309850
+300005
MAO-A deficiency
MECP2 duplication
%300260
Lubs
[3,4]
Pai (MRX64)
23
#252010
24
#304700
Mitochondrial
encephalomyopathy
Mohr-Tranebjaerg
25
26
27
#311150
#310400
+310600
%311050
Jensen
Myotubular myopathy
Norrie
OPA-2
28
#311250
OTC deficiency
29
30
311400
#312080
Paine / Seemanova
Pelizaeus-Merzbacher
#312920
Spastic paraplegia 2 /
SPG2
Baar-Gabriel
PGK1 deficiency
Plott
Pyruvate DH complex
E1 subunit deficiency
16
17
18
31
32
33
(312890)
*311800
308850
*312170
GRIA3 *305915
t(X;12)(q24;q15) in
one female
Xq25-q26
Optic atrophy, hearing loss, epilepsy, spasticity, restricted joint
mobility, early death
Hydrocephalus with stenosis of the aqueduct of Silvius
mental retardation, aphasia, shuffling gait, adducted thumbs
spastic paraplegia
L1CAM *308840
Xq22.1
ARHGEF9 *300429
Xq26.2
Xq23
HPRT *308000
DCX *300121
enzyme deficiency
Xp11.3
Xq28
MAOA +309850
MECP2 duplication
(+/-L1CAM)
enzyme deficiency
duplication (always
includes MECP2)
duplication (always
includes MECP2)
duplication (always
includes MECP2)
enzyme deficiency
Xq24
NDUFA1 *300078
Xq22.1
TIMM8A/DFN1
*300356
Xq28
Xp11.3
Xp11.4p11.21
Xp11.4
MTM1 *300415
NDP +310600
Xq22.2
OTC *300461
PLP *300401
bipolar disorder, epileptic seizures in infancy
partial agenesis of corpus callosum, Hirschsprung disease, spasticity,
short broad hands, facial anomalies
permanent hypertonia heightened by the slightest stimulus, sensory
hyperarousal, tonic seizures provoked by tactile stimulation
Cerebral palsy, choreoathetosis, self-distructive biting
Lissencephaly and epilepsy in males, subcortical laminar heterotopia
in some females
Aggressive behaviour, disturbance in monoamine metabolism
hypotonia, recurrent infections, spasticity and inability to walk, absent
speech, seizures, no microcephaly
congenital hypotonia, recurrent infections, early lethality
Epicanthus, high nasal bridge, small mouth, seizures, early lethality
Complex I deficiency
Hearing loss, visual impairment, ataxia, spastic paraplegia
Opticoacoustic nerve atrophy with dementia
Severe hypotonia, areflexia, generalized muscle weakness
Blindness, hearing loss
Optic atrophy, abnormal reflexes, dysarthria, tremor
enzyme deficiency
often gene
duplications
Xq21.1
PGK1 *311800
enzyme deficiency
Xp22.1
PDHA1 *312170
enzyme deficiency
Hyperammonemia
Spastic diplegia, myoclonic seizures, cerebellar hypoplasia
Spasticity, cerebellar ataxia, parkinsonism
Spastic paraplegia uncomplicated or complicated with nystagmus and
optic atrophy
Athetotic spastic paraplegia
Myoglobinuria, epilepsy, hemolytic anemia
Laryngeal abductor paralysis
Lactic acidosis, ataxia
34
35
#312750
Rett
Xq28
MECP2 +300005
dominant, lethal in
males
#300055
#300279
PPM-X / MRXS13
MR with progressive
spasticity
MRX
Reyniers/MRXS10
Xp11.22
HADH2 *300256
enzyme deficiency
#300458
#300220
#300438
Hydroxyacyl-CoA
dehydrogenase
deficiency, type II
SCAX2
36
302600
37
38
301790
%300266
39
%311510
40
41
#308350
#308350
#300432
#309510
#300215
SCAX3 / Schmidley
SPG16 (formerly SPG7) Xq11.2q23
Waisman-Laxova
Xq27.2qter
West, infantile spasms
Xp22.13
West, infantile spasms
Xp22.11
Myoclonic epilepsy
Partington /MRXS1
Berry-Kravis (XLAG)
#300004
Proud
42
%314580
Wieacker-Wolff
43
#300423
XMRE
Xp11.3q13
Xp11.4
44
45
46
[5]
[6]
[7]
Arena
Bertini
Goldblatt
(Xq22-q25)
Xp22.3
Xq22
47
[8]
Hamel BCD
48
[9]
Hildebrand
49
[10,11]
Passos-Bueno
Xp11.3q21.3
Xp11.3q21.3
Xp11.3q21.1
50
[12]
Tranebjaerg II
loss of language and purposeful movements, ataxia, autism,
dementia, microcephaly
Psychosis, pyramidal signs, macroorchidism
facial hypotonia, sialorrhea, spastic paraplegia, seizures, absent
language
nonspecific MR (MRX16, MRX79)
Choreoathetosis, dysarthria, retinal degeneration & near-blindness,
epilepsy, psychosis
ataxia, head tremor, unilateral sixth nerve palsy, spasticity and
extrapyramidal rigidity, cerebellar atrophy, early demise
Hypotonia, ataxia, sensorineural deafness, optic atrophy, early demise
Quadriplegia, motor aphasia, reduced vision, dysfunction of bowel and
bladder
Parkinsonism, seizures, apparent basal ganglia degeneration
STK9 *300203
ARX *300382
ATP6AP2 *300556
allelic to PLP ?
allelic to PLP ?
(quoted in SPG2
#312920) ?
Infantile spasms, hypsarrythmia
Infantile spasms, hypsarrythmia
myclonic epilepsy, spasticity, developmental delay from birth
Dysarthria, dystonic hand movements, ataxia, seizures
Lissencephaly with frontal pachygiria and posterior agyria, agenesis of
corpus callosum, neonatal intractable epilepsy and severe hypotonia,
hypothalamic dysfunction with frequent hypothermia, ambiguous
genitalia
Microcephaly, agenesis of corpus callosum, arthrogryposis, renal
dysplasia, hypospadias
Contractures, distal muscular atrophy, dyspraxia of ocular and facial
muscles
Generalized tonic-clonic and atonic seizures, moderate MR, normal
electromyography and nerve conduction
Spastic paraplegia, ataxia, titubation, iron deposits in basal ganglia
Ataxia, hypotonia, recurrent infections
spastic paraplegia, nystagmus, optic atrophy, muscle hypoplasia
Blindness, convulsions, hypomyelination, spasticity, early death
severe congenital deafness, no dysmorphism, normal growth
allelic to AHD
#300523?
Spastic paraplegia, muscle hypoplasia, severe MR
Dyspraxia, ataxia, seizures, pes equinovarus, macroorchidism
51
[13]
Vles
L1CAM?
Corpus callosum agenesis, spastic quadriparesis, irregular lining of
lateral ventricles
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