distal muscle atrophy

Ataxia with Oculomotor Apraxia 3

Clinical Characteristics
Ocular Features: 

Ocular movement abnormalities are noted at the same time as other peripheral motor difficulties.  Slow saccadic eye movements, and head-eye lag are evident.  Pursuit movements are normal.

Systemic Features: 

Onset of gait instability occurs in the second decade of life with dysmetria and frequent falls. The eye movement abnormalities, dysarthria, and axial dysmetria with distal muscle atrophy and weakness are present at the same time.  Distal sensory deficits with lack of sensory nerve action potentials are also present in the lower limbs.  The upper limbs are involved somewhat later but with less pronounced movement impairment.  Hyporeflexia or areflexia is common.  The disorder is progressive with loss of independent mobility by the third decade.

Brain and spinal cord MRI imaging reveals cerebellar atrophy of the folia and vermis.  Persistently elevated alpha-fetoprotein levels have been found but no hypoalbuminemia.

Genetics

Homozygous missense mutations in the PIK3R5 gene (17p12-p13) have been associated with this clinical picture in one family of 4 affected sibs born of consanguineous parents.

See also Ataxia with Oculomotor Apraxia 1 (208920) with hypoalbuminemia, Ataxia with Oculomotor Apraxia 2 (606002) (also known as Spinocerebellar Ataxia, Autosomal Recessive 1 or SCAR1), and Ataxia with Oculomotor Apraxia 4 (616267).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment has been reported.

References
Article Title: 

Spastic Paraplegia 75

Clinical Characteristics
Ocular Features: 

Nystagmus with optic atrophy is usually present and one individual had glaucoma. 

Systemic Features: 

This is an early-onset and progressive neurodegenerative disorder.  Hypotonia may be present at birth.  A spastic gait and difficulty walking is noted in early childhood and most individuals never walk unassisted. Yong adults have spastic paresis with extensor plantar responses and clonus has been reported.  Distal muscle atrophy in the lower extremities has been noted.  Speech is dysarthric.  Brain imaging has been normal in some patients whereas others have mild atrophy of the cerebellum and the corpus callosum.  Cognitive impairment is variable with some individuals showing poor school performance while others are described as mentally retarded.

Genetics

Homozygous mutations in the MAG gene (19q13.12) are responsible for this disorder.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No effective treatment has been reported although physical therapy may be helpful. Special education, speech and physical therapy, and low vision devices might also be of benefit.

References
Article Title: 

Myelin-associated glycoprotein gene mutation causes Pelizaeus-Merzbacher disease-like disorder

Lossos A, Elazar N, Lerer I, Schueler-Furman O, Fellig Y, Glick B, Zimmerman BE, Azulay H, Dotan S, Goldberg S, Gomori JM, Ponger P, Newman JP, Marreed H, Steck AJ, Schaeren-Wiemers N, Mor N, Harel M, Geiger T, Eshed-Eisenbach Y, Meiner V, Peles E. Myelin-associated glycoprotein gene mutation causes Pelizaeus-Merzbacher disease-like disorder. Brain. 2015 Sep;138(Pt 9):2521-36.

PubMed ID: 
26179919

Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders

Novarino G, Fenstermaker AG, Zaki MS, Hofree M, Silhavy JL, Heiberg AD, Abdellateef M, Rosti B, Scott E, Mansour L, Masri A, Kayserili H, Al-Aama JY, Abdel-Salam GM, Karminejad A, Kara M, Kara B, Bozorgmehri B, Ben-Omran T, Mojahedi F, Mahmoud IG, Bouslam N, Bouhouche A, Benomar A, Hanein S, Raymond L,Forlani S, Mascaro M, Selim L, Shehata N, Al-Allawi N, Bindu PS, Azam M, Gunel M, Caglayan A, Bilguvar K, Tolun A, Issa MY, Schroth J, Spencer EG, Rosti RO, Akizu N, Vaux KK, Johansen A, Koh AA, Megahed H, Durr A, Brice A, Stevanin G, Gabriel SB, Ideker T, Gleeson JG. Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders. Science. 2014 Jan 31;343(6170):506-11.

PubMed ID: 
24482476
Subscribe to RSS - distal muscle atrophy