Dysequilibrium Syndrome

Dysequilibrium syndrome (DES) is a non-progressive cerebellar disorder characterized by ataxia associated with an intellectual disability, delayed ambulation and cerebellar hypoplasia.

Epidemiology

To date, more than 50 individuals have been reported in the world literature.

Clinical description

DES is a congenital disorder characterized by nonprogressive cerebellar ataxia, associated with a moderate to profound intellectual disability and delayed ambulation. Gait can be either bipedal or quadrupedal. Additional features include hypotonia, lack of coordination, delayed motor development, seizures, dysarthria, strabismus, short stature and pes planus.

Etiology

Etiological subtypes of DES have been reported and include type 1 (CAMRQ1), 2 (CAMRQ2), 3 (CAMRQ3) and 4 (CAMRQ4) which are attributed to mutations in VLDLR (9p24), CA8 (8q12.1), WDR81 (17p13.3) and ATP8A2 (13q12) genes, respectively. VLDLR encodes the very low density lipoprotein receptor (VLDLR) which is involved in neuronal migration in the cerebral cortex and cerebellum. CA8 encodes a carbonic-anhydrase related protein, whose biological function is not yet fully understood. The function of WDR81 is still unknown. ATP8A2 encodes an ATPase which is mainly expressed in brain tissue, with the highest levels found in the cerebellum, and that may be critical for the developmental processes of the central nervous system.

Genetic counseling

Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them of the 25% risk of having an affected child.