gait anomalies

Neurodevelopmental Disorder With or Without Seizures and Gait Abnormalities

Clinical Characteristics
Ocular Features: 

Nystagmus and strabismus are common ocular features.  Optic nerve hypoplasia is present in some individuals.

Systemic Features: 

Symptoms may begin in early infancy or childhood.  Several neonates with irritability, hypertonia, increased startle reflexes, and stiffness have been reported.  Hypotonia may occur in the neonatal period though.  Intellectual disability and severe developmental delay are common and some patients are unable to follow simple commands.  Seizures of variable severity frequently occur at some point.  Speech may be absent.  Some patients are unable to walk while those that do have a clumsy, spastic gait.  Joint contractures may develop.

The most obvious dysmorphic feature are large ears.  Choreiform and stereotypic hand movements are sometimes present.  Feeding difficulties and sleeping problems may be noted.  Cortical atrophy and thinning of the corpus callosum has been seen on brain imaging.  One mildly affected individual was short in stature.

Genetics

Heterozygous mutations in the GRIA4 gene (11q22.3) have been found in 5 unrelated patients.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No treatment has been reported.

References
Article Title: 

Spastic Paraplegia 11

Clinical Characteristics
Ocular Features: 

Gaze evoked nystagmus and pigmentation in the macula are components of this syndrome and adults have some degree of retinal degeneration with poor vision eventually.  Optic atrophy and ptosis have been reported but rarely.   

Systemic Features: 

his progressive condition nay have its onset in childhood or early adolescence although rarely it first appears in adulthood.  Obesity is a component in older individuals.  Loss of ambulation usually occurs within 10 years of the onset of gait difficulties.  Hyperreflexia and spasticity develop early while ataxia, urinary sphincter disturbances, extensor plantar responses, and dysarthria appear later.  Amyotrophy is frequently seen in the thenar and hypothenar muscles.  Children have learning difficulties while cognitive decline and frank mental retardation occur somewhat later.  

Peripheral nerve biopsy may reveal hypomyelination and loss of unmyelinated nerve fibers.  MRI imaging in some individuals shows a thin or absent corpus callosum and cortical atrophy. 

Genetics

Homozygous mutations in the gene SPG11 (15q21.1) encoding spatacsin are responsible for this disorder. 

See spastic paraplegia 15 (Kjellin syndrome) (270700) and spastic paraplegia 7 (607259) for other disorders with retinal degeneration, optic atrophy, and nystagmus.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

None known.

References
Article Title: 

Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum

Stevanin G, Santorelli FM, Azzedine H, Coutinho P, Chomilier J, Denora PS, Martin E, Ouvrard-Hernandez AM, Tessa A, Bouslam N, Lossos A, Charles P, Loureiro JL, Elleuch N, Confavreux C, Cruz VT, Ruberg M, Leguern E, Grid D, Tazir M, Fontaine B, Filla A, Bertini E, Durr A, Brice A. Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum. Nat Genet. 2007 Mar;39(3):366-72.

PubMed ID: 
17322883
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