CMARQ3 is a congenital cerebellar ataxia characterized by quadrupedal gait, in which affected persons walk on all four extremities. Although the affected persons could stand upright and even walk bipedally, they prefer quadrupedal walking. Additionally, this syndrome is associated with dysarthia and mild mental retardation.
Turkmen et al. (2009) reported a consanguineous Iraqi family in which four of eight sibs had congenital ataxia, mild mental retardation, and dysarthria. All walked with a quadrupedal gait, with straight legs and placing their weight on the palms of their hands. The parents claimed that the affected persons never learned to crawl on their knees as most infants do, but ambulated from infancy on with their legs held straight with a 'bear-like' gait. Attempts to teach the children to walk on two legs with crutches or other supports failed. All complained of lack of balance and frequent falls when trying to walk bipedally. There were no other neurologic symptoms. Brain imaging was not performed, but Turkmen et al. (2009) speculated that the ataxia resulted from cerebellar dysfunction based on an animal model. At molecular level, Turkmen et al. (2009) identified a homozygous mutation in the CA8 gene (c.298T>C; S100P) on chromosome 8q12, by carrying out genome-wide linkage analysis followed by candidate gene sequencing of this family.
Kaya et al. (2011) described seven patients with cerebellar ataxia, mental retardation (MR), and disequilibrium syndrome type 3 from there related families. The first family had only one affected member (proband), the second family had four affected members (3 males and one female), and the third family had two affected members (one male and one female). The parents of the first and second families were siblings, and the third family was closely related. The proband was a 9-year-old boy born to consanguineous Saudi parents. Linkage analysis showed a peak on chromosome 8q12.1–8q13.3 with a LOD score of 5.1, that harbors the CA8 gene in which a novel homozygous c.484G>A (p.G162R) mutation in exon 4 was identified in all seven patients. The parents of the three families were heterozygous for the same mutation. This mutation was not found in 200 unrelated healthy Saudi controls.