Autosomal recessive spastic paraplegia type 43

General Information (adopted from Orphanet):

Synonyms, Signs: SPG43
Number of Symptoms 18
OrphanetNr: 320370
OMIM Id: 615043
ICD-10: G11.4
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 2 cases
Inheritance:
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: Autosomal recessive complex spastic paraplegia
 -Rare genetic disease
 -Rare neurologic disease

Comment:

2 sisters of consanguineous Malian parents has been identified with a homozygous missense mutation in the C19ORF12 gene, position c.187G>C predicting the amino acid substitution p.Ala63Pro. In a consanguineous Brazilian family, two affected siblings carry the same mutation p.Ala63Pro. This C19orf12-p.A63P mutation can present with or without typical features of NBIA (neurodegeneration with brain iron accumulation), i.e., that it can cause spastic paraplegia with lower motor neuron features (SPG43) without vision loss and brain iron accumulation, as in the Malian family, or with vision loss and evidence of brain iron accumulation but without extrapyramidal features (dystonia and parkinsonism), as in the Brazilian family (PMID:23857908).

Symptom Information: Sort by abundance 

1
(HPO:0001288) Gait disturbance 23857908 IBIS 318 / 7739
2
(HPO:0009830) Peripheral neuropathy 23857908 IBIS 206 / 7739
3
(HPO:0001284) Areflexia 23857908 IBIS 198 / 7739
4
(HPO:0001265) Hyporeflexia 23857908 IBIS 208 / 7739
5
(HPO:0001257) Spasticity 23857908 IBIS 251 / 7739
6
(HPO:0001258) Spastic paraplegia 20039086 IBIS 97 / 7739
7
(HPO:0002936) Distal sensory impairment 23857908 IBIS 96 / 7739
8
(HPO:0007149) Distal upper limb amyotrophy 20039086 IBIS 4 / 7739
9
(HPO:0008954) Intrinsic hand muscle atrophy 20039086 IBIS 2 / 7739
10
(HPO:0006380) Knee flexion contracture 20039086 IBIS 56 / 7739
11
(HPO:0006466) Ankle contracture 20039086 IBIS 17 / 7739
12
(HPO:0008959) Distal upper limb muscle weakness 23857908 IBIS 3 / 7739
13
(HPO:0003693) Distal amyotrophy 20039086 IBIS 118 / 7739
14
(HPO:0009053) Distal lower limb muscle weakness 23857908 IBIS 13 / 7739
15
(HPO:0012785) Flexion contracture of finger 20039086 IBIS 3 / 7739
16
(OMIM) Distal muscle weakness, upper and lower limbs 23857908 IBIS 4 / 7739
17
(OMIM) Contractures of the fingers 20039086 IBIS 3 / 7739
18
(OMIM) Difficulties in fine movement of the hands 23857908 IBIS 1 / 7739

Associated genes:

C19orf12;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Spastic paraplegia-43 (SPG43) is an autosomal recessive neurodegenerative disorder characterized by childhood onset of progressive spasticity affecting the lower and upper limbs (summary by Meilleur et al., 2010).

For a general phenotypic description and a discussion ...

Clinical Description OMIM Meilleur et al. (2010) reported 2 sisters from Mali with childhood-onset spastic paraplegia. The girls had onset at ages 7 and 12 years, respectively, of difficulty walking due to progressive spasticity of the lower limbs. Physical examination of ...
Molecular genetics OMIM In 2 sisters, born of consanguineous Malian parents, originally reported by Meilleur et al. (2010) as having autosomal recessive SPG43, Landoure et al. (2013) identified a homozygous missense mutation in the C19ORF12 gene (A63P; 614297.0006). The mutation was ...