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.


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

Treatment Options: 

No treatment has been reported.

Article Title: 


Martin S, Chamberlin A, Shinde DN, Hempel M, Strom TM, Schreiber A, Johannsen J, Ousager LB, Larsen MJ, Hansen LK, Fatemi A, Cohen JS, Lemke J, Sorensen KP, Helbig KL, Lessel D, Abou Jamra R. De Novo Variants in GRIA4 Lead to Intellectual Disability with or without Seizures and Gait Abnormalities. Am J Hum Genet. 2017 Dec 7;101(6):1013-1020.

PubMedID: 29220673