sensory impairment

Myopathy, Mitochondrial Anomalies, and Ataxia

Clinical Characteristics
Ocular Features: 

Ocular findings are variable.  One of three individuals with compound heterozygous mutations had a pigmentary retinopathy with pallor of the optic nerve but no visual abnormalities.  Her sister had only optic nerve pallor.  The eyes are described as "small" and "close-set".

No ocular findings were reported for the family with autosomal dominant inheritance.

Systemic Features: 

Ataxia, short stature, and gait difficulties from an early age are consistent findings.  Some patients are never able to walk.  Motor development is generally delayed.  Truncal and limb ataxia is a feature.  Some degree of intellectual disability is generally present and speech is often delayed.  

The face is long with a myopathic appearance.  Both micrognathia and a prominent jaw may be seen.  The palate is highly arched.  Patients are described as hypotonic and there is generalized muscle weakness both proximal and distal.  Distal sensory impairment has been described in the family with presumed dominant inheritance and there may be psychiatric symptoms of anxiety, depression, and schizophrenia.  Dysmetria with dysdiadochokinesis is often present and a fine intention tremor has been observed.

Mitochondria in fibroblasts exhibit abnormal dynamics and occur in a fragmented network.  Muscle biopsies reveal changes consistent with myopathy.  Serum creatine kinase may be elevated.

Genetics

Compound heterozygous mutations in the MSTO1 gene (1q22) have been found in two families with 3 affected individuals suggesting autosomal recessive inheritance.  In a third family, heterozygous mutations in the same gene were found in a mother and 3 of her adult children, consistent with autosomal dominant transmission.

Pedigree: 
Autosomal dominant
Autosomal recessive
Treatment
Treatment Options: 

No treatment has been reported.

References
Article Title: 

Spastic Paraplegia 74

Clinical Characteristics
Ocular Features: 

Onset of visual impairment occurs at ages of 10-14 years with optic pallor evident on fundoscopy. MRI imaging reveals physical atrophy of the optic nerve.  Visual acuity ranges from 0.5 to finger counting.  Visual field defects include central scotomas and peripheral concentric constriction.

Systemic Features: 

Symptoms consisting of a spastic gait and distal sensory impairment usually appear in the first decade and are slowly progressive.  Increased deep tendon reflexes and extensor plantar responses may be present at that time but later distal leg muscle atrophy and pes cavus appear.  The ankle reflexes later disappear.  Cognitive function is normal and adults are able to lead an independent life.

Nerve conduction studies in 4 individuals showed reduced muscle action potentials and velocity while sensory conduction was normal.  Cerebellar atrophy along with an attenuated corpus callosum and cervical spinal cord atrophy was noted on MRI imaging in one of 3 studied patients.

Genetics

A homozygous splice site mutation in IBA57 (1q42) has been found to segregate with this condition in a large consanquineous Arab family.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment is known for the basic disease but physical therapy and low vision aids are likely beneficial.

References
Article Title: 

Fe S protein assembly gene IBA57 mutation causes hereditary spastic paraplegia

Lossos A, Stumpfig C, Stevanin G, Gaussen M, Zimmerman BE, Mundwiller E, Asulin M, Chamma L, Sheffer R, Misk A, Dotan S, Gomori JM, Ponger P, Brice A, Lerer I, Meiner V, Lill R. Fe/S protein assembly gene IBA57 mutation causes hereditary spastic paraplegia. Neurology. 2015 Feb 17;84(7):659-67.

PubMed ID: 
25609768
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