Heterozygous variants in : Beyond congenital mirror movements.

OBJECTIVE

To perform a comprehensive characterization of a cohort of patients with congenital mirror movements (CMMs) in Sweden.

METHODS

Clinical examination with the Woods and Teuber scale for mirror movements (MMs), neuroimaging, navigated transcranial magnetic stimulation (nTMS), and massive parallel sequencing (MPS) were applied.

RESULTS

The cohort is ethnically diverse and includes a total of 7 patients distributed in 2 families and 2 sporadic cases. The degree of MMs was variable in this cohort. MPS revealed 2 novel heterozygous frameshift variants in DCC netrin 1 receptor (). Two siblings harboring the pathogenic variant in c.1466_1476del display a complex syndrome featuring MMs and in 1 case receptive-expressive language disorder, chorea, epilepsy, and agenesis of the corpus callosum. The second variant, c.1729delG, was associated with a typical benign CMM phenotype. No variants in , , , or were found for the 2 sporadic CMM cases. However, one of these sporadic cases had concomitant high-risk myelodysplastic syndrome and a homozygous variant in ERCC excision repair like 2 (). Reorganized corticospinal projection patterns to upper extremities were demonstrated with nTMS.

CONCLUSIONS

The presence of chorea expands the clinical spectrum of syndromes associated with variants in . Biallelic pathogenic variants in cause bone marrow failure, but a potential association with CMM remains to be studied in larger cohorts.