#613206
Table of Contents
A number sign (#) is used with this entry because of evidence that autosomal recessive spastic paraplegia-44 (SPG44) is caused by homozygous mutation in the GJC2 gene (608803) on chromosome 1q42. One such family has been reported.
Orthmann-Murphy et al. (2009) reported 3 members of a large Italian family with spastic paraplegia. Although mild symptoms were reported in the first or second decades, there was more severe progression with disability in the third decade. Physical examination at age 39, 36, and 53 years, respectively, showed lower limb spasticity, spastic gait, extensor plantar responses, hyperreflexia, and pes cavus. One patient used a walker, and 1 was wheelchair-bound. Other features included dysarthria, loss of finger dexterity, dysmetria, and intention tremor on finger-to-nose and heel-to-knee testing. Nystagmus was not present. One patient had lumbar hyperlordosis, and another had scoliosis. The 39-year-old proband presented with an 8-year history of slowly progressive walking difficulties, leg stiffness, and slurred speech. He reported feelings of clumsiness since his teens but was fit for military service at age 18. His 36-year-old brother had minimal motor difficulties since infancy and mild learning impairment at school. He also reported mild intention tremor during late-childhood and a few tonic-clonic seizures, mainly febrile, between childhood and his early teens. A 53-year-old female cousin had earlier onset in her teens and was wheelchair-bound by age 30. She had mild cognitive impairment. In her forties, she developed urinary incontinence, episodic painful spasms in the lower limbs, and constipation. At the time of the report, she had upper limb involvement, decreased sensation in the limbs, severe dorsal scoliosis, bilateral pes cavus, and ankle contractures. Brain MRI showed a hypomyelinating leukodystrophy and thin corpus callosum in all 3 patients. Central nerve conduction studies (motor evoked potentials, MEP) were prolonged in all patients, but peripheral nerve conduction was normal.
The transmission pattern of SPG44 in the family reported by Orthmann-Murphy et al. (2009) was consistent with autosomal recessive inheritance.
In 3 affected members of an Italian family with SPG44, Orthmann-Murphy et al. (2009) identified a homozygous mutation in the GJC2 gene (I33M; 608803.0008). Heterozygous family members were unaffected. The authors noted that the phenotype was less severe than hypomyelinating leukoencephalopathy-2 (HLD2; 608804), an allelic disorder.
Orthmann-Murphy, J. L., Salsano, E., Abrams, C. K., Bizzi, A., Uziel, G., Freidin, M. M., Lamantea, E., Zeviani, M., Scherer, S. S., Pareyson, D. Hereditary spastic paraplegia is a novel phenotype for GJA12/GJC2 mutations. Brain 132: 426-438, 2009. [PubMed: 19056803, images, related citations] [Full Text]
SNOMEDCT: 723821002; ORPHA: 320401; DO: 0110796;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 1q42.13 | ?Spastic paraplegia 44, autosomal recessive | 613206 | Autosomal recessive | 3 | GJC2 | 608803 |
A number sign (#) is used with this entry because of evidence that autosomal recessive spastic paraplegia-44 (SPG44) is caused by homozygous mutation in the GJC2 gene (608803) on chromosome 1q42. One such family has been reported.
Orthmann-Murphy et al. (2009) reported 3 members of a large Italian family with spastic paraplegia. Although mild symptoms were reported in the first or second decades, there was more severe progression with disability in the third decade. Physical examination at age 39, 36, and 53 years, respectively, showed lower limb spasticity, spastic gait, extensor plantar responses, hyperreflexia, and pes cavus. One patient used a walker, and 1 was wheelchair-bound. Other features included dysarthria, loss of finger dexterity, dysmetria, and intention tremor on finger-to-nose and heel-to-knee testing. Nystagmus was not present. One patient had lumbar hyperlordosis, and another had scoliosis. The 39-year-old proband presented with an 8-year history of slowly progressive walking difficulties, leg stiffness, and slurred speech. He reported feelings of clumsiness since his teens but was fit for military service at age 18. His 36-year-old brother had minimal motor difficulties since infancy and mild learning impairment at school. He also reported mild intention tremor during late-childhood and a few tonic-clonic seizures, mainly febrile, between childhood and his early teens. A 53-year-old female cousin had earlier onset in her teens and was wheelchair-bound by age 30. She had mild cognitive impairment. In her forties, she developed urinary incontinence, episodic painful spasms in the lower limbs, and constipation. At the time of the report, she had upper limb involvement, decreased sensation in the limbs, severe dorsal scoliosis, bilateral pes cavus, and ankle contractures. Brain MRI showed a hypomyelinating leukodystrophy and thin corpus callosum in all 3 patients. Central nerve conduction studies (motor evoked potentials, MEP) were prolonged in all patients, but peripheral nerve conduction was normal.
The transmission pattern of SPG44 in the family reported by Orthmann-Murphy et al. (2009) was consistent with autosomal recessive inheritance.
In 3 affected members of an Italian family with SPG44, Orthmann-Murphy et al. (2009) identified a homozygous mutation in the GJC2 gene (I33M; 608803.0008). Heterozygous family members were unaffected. The authors noted that the phenotype was less severe than hypomyelinating leukoencephalopathy-2 (HLD2; 608804), an allelic disorder.
Orthmann-Murphy, J. L., Salsano, E., Abrams, C. K., Bizzi, A., Uziel, G., Freidin, M. M., Lamantea, E., Zeviani, M., Scherer, S. S., Pareyson, D. Hereditary spastic paraplegia is a novel phenotype for GJA12/GJC2 mutations. Brain 132: 426-438, 2009. [PubMed: 19056803] [Full Text: https://doi.org/10.1093/brain/awn328]
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