Background: Mirror movements (MM) are frequently associated to Kallmann syndrome (KS). They are mainly observed in patients with ANOS1 (KAL1) mutations. MM have never been reported in ANOS1 mutated females. A defect in the contralateral inhibition of the pyramidal tract has been proposed as the mechanism of MM in KS but never demonstrated.
Objective and hypotheses: To investigate the molecular mechanism of a familial case of gonadotropic deficiency in which 11 males had KS whereas females were diagnosed with MM (family 1). To test the hypothesis that MM in KS may be due to an abnormal development of the pyramidal tracts.
Method: Patients with KS were investigated for ANOS1 mutations. The pyramidal tracts were analysed by imaging (diffusion tensor imaging tractography) in an adult with ANOS1 mutation and by neuropathology in a mutated foetus.
Results: A complex rearrangement in ANOS1 was found in male and female members of family 1 (C2067_2070AGGA>TCCT; p.Glu642Alafs21), one nonsense mutation in an adult (c.773G>A; p.Trp258X) and one mutation in a foetus (c.769C>T; p.Arg257X) who had been medically terminated for bilateral renal agenesis with cleft lip and palate. The tractography showed a lack of decussation of the pyramidal tracts in the adult proband. Pathology examination of the foetus revealed hypoplastic and abnormally shaped corticospinal tracts in the pons and medulla.
Conclusion: We show clinical, imaging technique and anatomical evidence of MM in KS caused by ANOS1 mutation. Congenital MM may be transmitted as a dominant trait in ANOS1 mutated patients. ANOSMIN is involved in guidance and development of corticospinal axons, as already known for olfactory axons.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology