Mirror Movements 3

A number sign (#) is used with this entry because of evidence that congenital mirror movements-3 (MRMV3) is caused by homozygous mutation in the DNAL4 gene (610565) on chromosome 22q13. One such family has been reported.

For a phenotypic description and a discussion of genetic heterogeneity of mirror movements, see MRMV1 (157600).

Clinical Features

Ahmed et al. (2014) reported a large consanguineous Pakistani family in which 11 individuals spanning 5 generations had congenital mirror movements exclusively and predominantly affecting the hands and fingers; proximal upper limbs and lower limbs were not affected. The amplitude of movement for mirroring was generally less compared to voluntary movement, and affected individuals could partially suppress the movements. Situs inversus was not present in 3 affected individuals who were tested, and none of the patients had evidence of defective mucociliary clearance. The onset of symptoms was typically noted around 2 to 3 years of age, but some patients were noted to have symptoms as early as 2 to 3 months of age. Pain and/or cramping during manual activities was not reported.

Inheritance

The transmission pattern of MRMV3 in the family reported by Ahmed et al. (2014) was consistent with autosomal recessive inheritance.

Molecular Genetics

In affected members of a consanguineous Pakistani family with congenital mirror movements, Ahmed et al. (2014) identified a homozygous splice site mutation in the DNAL4 gene (610565.0001), resulting in the in-frame deletion of 28 conserved residues. The mutation was found by a combination of homozygosity mapping and whole-exome sequencing. Functional studies of the variant were not performed, but Ahmed et al. (2014) noted that because the DNAL4 gene is thought to be part of the axonemal complex of dynein molecules, the mutation may interrupt protein interactions and cause disruption of dynein function, resulting in abnormal directional axonal growth. Disruption of axonal growth could affect commissural neurons of the corpus callosum, resulting in faulty cross-brain wiring and MRMV.