Cerebral Atrophy, Autosomal Recessive

Clinical Characteristics
Ocular Features: 

Severe visual impairment is noted before one year of age when infants cease following objects in their environment.  Cortical visual impairment has been diagnosed although 'atrophic optic fundi' and hypotrophic optic nerves and fovea have also been described.  Nystagmus has been observed as well.

Systemic Features: 

Microcephaly relative to age norms is evident usually by 2 months of age and there is little subsequent growth of the skull.  Regression of developmental milestones is noted by 4 months of age with signs of irritability, akathisia, spasticity, visual impairment, seizures, and increased startle responses.  Sucking responses and eye-to-eye contact are usually lost by 6 months of age.  Repetitive body stiffening and extension of arms in older individuals consistent with seizure activity has been confirmed by EEG in at least one infant.  Imaging consistently reveals cerebral atrophy with ventriculomegaly and general loss of brain volume. Progressive muscle weakness is evident after about 1 year of age and oral feeding is impaired. There is complete lack of responsive interaction beyond irritability and agitation while motor function is limited to involuntary responses.  Two individuals have lived into the second decade of life.


This condition has been described in 4 individuals who were products of consanquineous Amish couples.  Homozygous mutations in the TMPRSS4 gene (11q23.3), whose product is a serine transmembrane protease, seems to be responsible.

Treatment Options: 

No treatment is known.

Article Title: 


Lahiry P, Racacho L, Wang J, Robinson JF, Gloor GB, Rupar CA, Siu VM, Bulman DE, Hegele RA. A mutation in the serine protease TMPRSS4 in a novel pediatric neurodegenerative disorder. Orphanet J Rare Dis. 2013 Aug 17;8:126.

PubMedID: 23957953