Here is a summary of the paper on hereditary PLS. This is the only documented case I have heard of. I am in a PLS study group. I'll ask my coordinator if she has heard of any cases.
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Arch Neurol. 2008 Mar;65(3):383-6. doi: 10.1001/archneur.65.3.383.
A locus for primary lateral sclerosis on chromosome
4ptel-4p16.1.
Valdmanis PN, Dupré N, Rouleau GA.
Source
Department of Human Genetics, McGill
University, Montreal, Quebec, Canada.
Abstract
BACKGROUND:
Primary lateral sclerosis (PLS) is
an adult-onset upper motor neuron disease resulting in spinal and bulbar
spasticity. A family with 8 individuals diagnosed with PLS was previously
reported.
OBJECTIVE:
To identify a locus for a large
family with PLS.
METHODS:
A 550-marker whole-genome scan was
performed on this family followed by fine mapping with sequence-tagged site
markers to identify a candidate region.
RESULTS:
A locus was identified for this
family between the telomere of chromosome 4 and marker D4S2928 (4ptel-4p16.1).
A maximum lod score of 3.01 was obtained for marker D4S2936. The region spans
23.17 cM (10.2 megabase pairs) and encompasses 130 genes.
CONCLUSIONS:
PLS1
does not map near any other identified loci for upper or lower motor neuron
diseases and thus represents a novel locus for PLS.
Â
The following is from the OMIN site:
PRIMARY LATERAL SCLEROSIS, ADULT, 1; PLSA1
Alternative titles; symbols
PLS, ADULT; PLSA
Cytogenetic location: 4p16 Â Â Genomic coordinates (GRCh37): 4:0 - 11,300,000
(from NCBI)
Gene Phenotype Relationships
Location Phenotype Phenotype
MIM number
4p16 Primary lateral sclerosis, adult, 1 611637
Clinical Synopsis
TEXT
Description
Although primary lateral sclerosis (PLS) is similar to amyotrophic lateral
sclerosis (ALS; 105400), they are considered to be clinically distinct
progressive paralytic neurodegenerative disorders. Following a period of
diagnostic confusion, the clinical distinction between ALS and PLS became clear
and diagnostic criteria were established (Pringle et al., 1992). PLS is
characterized by degeneration of the upper motor neurons and the corticospinal
and corticobulbar tracts, whereas ALS is a more severe disorder characterized by
degeneration of both the upper and lower motor neurons.
See 606353 for autosomal recessive juvenile-onset PLS, which is caused by
mutations in the ALS2 gene (606352).
Clinical Features
Pringle et al. (1992) reported 8 unrelated patients with adult-onset sporadic
PLS and suggested diagnostic criteria. Clinical features were limited to those
associated with the descending motor tracts and included spastic tetraparesis,
pseudobulbar affect, spastic dysarthria, hyperreflexia, and extensor plantar
responses. The mean age at onset was 50 years, and the disorder was slowly
progressive. Neuropathologic findings showed selective involvement of the motor
cortex with atrophy of pyramidal cells and degeneration of the lateral
corticospinal tracts. Lower motor neurons were spared.
Dupre et al. (2007) reported a 3-generation French-Canadian family in which 8
living members had primary lateral sclerosis inherited in an autosomal dominant
pattern. Four decreased family members were reportedly affected. Age at onset
ranged from 30 to 60 years, with an average of 48.4 years. The disorder began
with progressive asymmetric spastic paraparesis and weakness of the lower limbs
followed by upper limb involvement. Bulbar symptoms developed later with spastic
dysarthria and dysphagia. Reflexes were diffusely increased and sensation was
normal. Nerve conduction abnormalities consistent with an axonal neuropathy
occurred in some patients later in the disease. Brain MRI was normal in all, but
2 patients showed mild spinal cord atrophy. The disorder appeared to involve
only upper motor neurons. Linkage analysis excluded multiple loci including
ALS2.
Mapping
By genomewide scanning of a large French Canadian family with adult PLS (Dupre
et al., 2007), Valdmanis et al. (2008) identified a 23.17-cM candidate region on
chromosome 4ptel-4p16.1 (maximum lod score of 3.01 at D4S2936) that they termed
PLS1.
Molecular Genetics
Exclusion Studies
Brugman et al. (2007) found no mutations in the ALS2 gene among 51 presumably
unrelated Dutch patients with adult-onset PLS.
In a large French Canadian family with adult PLS, Valdmanis et al. (2008)
excluded mutations in the MYL5 gene (160782) by molecular analysis.
Nomenclature
Valdmanis et al. (2008) referred to the locus on chromosome 4ptel-p16.1 as
'PLS1'; however, this symbol has been reserved for the plastin-1 gene (602734).
REFERENCES
1. Brugman, F., Eymard-Pierre, E., van den Berg, L. H., Wokke, J. H. J.,
Gauthier-Barichard, F., Boespflug-Tanguy, O. Adult-onset primary lateral
sclerosis is not associated with mutations in the ALS2 gene. Neurology 69:
702-704, 2007. [PubMed: 17698795, related citations] [Full Text: HighWire Press]
2. Dupre, N., Valdmanis, P. N., Bouchard, J.-P., Rouleau, G. A. Autosomal
dominant primary lateral sclerosis. Neurology 68: 1156-1157, 2007. [PubMed:
17404201, related citations] [Full Text: HighWire Press]
3. Pringle, C. E., Hudson, A. J., Munoz, D. G., Kiernan, J. A., Brown, W. F.,
Ebers, G. C. Primary lateral sclerosis: clinical features, neuropathology and
diagnostic criteria. Brain 115: 495-520, 1992. [PubMed: 1606479, related
citations] [Full Text: HighWire Press]
4. Valdmanis, P. N., Dupre, N., Rouleau, G. A. A locus for primary lateral
sclerosis on chromosome 4ptel-4p16.1. Arch. Neurol. 65: 383-386, 2008. [PubMed:
18332252, related citations] [Full Text: HighWire Press]
