ATP7A mutation with occipital horns and distal motor neuropathy: A continuum

Melanie Fradin (1, 2) , Alinoe Lavillaureix (3, 2, 1) , Sylvie Jaillard (1) , Chloe Quelin (1, 2) , Paul Sauleau (1) , Marie-Christine Minot (1) , Dominique Menard (1) , Gilles Edan (4, 1) , Irene Ceballos (5) , Catherine Tréguier (1) , Maia Proisy (1) , Corinne Magdelaine (6) , A.-S. Lia (6) , Sylvie Odent (3, 2) , Laurent Pasquier (1, 2)

1 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
2 Centre de référence Maladies Rares CLAD-Ouest [Rennes]
3 IGDR - Institut de Génétique et Développement de Rennes
4 CIC - Centre d'Investigation Clinique [Rennes]
5 Hôpital Necker - Enfants Malades [AP-HP]
6 CHU Limoges

ATP7A-related copper transport disorders are classically separated in three pathologies according to their severity, all inherited in an X-linked recessive manner: Menkes disease (MD, OMIM #309400) which represent more than 90% of cases; occipital Horn Syndrome (OHS, OMIM #304150) and ATP7A-related distal motor neuropathy also named X-linked distal spinal muscular atrophy-3 (SMAX3, OMIM #300489) (Kennerson et al., 2010). Although there is no clear cut correlation between Cu and ceruloplasmin levels in ATP7A related disorders, these three entities probably represent a continuum partly depending on residual functional ATP7A protein (Møller, 2015). Thus far OHS and SMAX3 only partially overlap. In fact patients with OHS usually have no distal motor neuropathy signs but, on the other hand, occipital horns, which are the main sign of OHS, have not been described in SMAX3 patient. We describe here a patient bearing a missense ATP7A mutation with associated signs of distal motor neuropathy as well as occipital horns, confirming that OHS and SMAX3 are a continuum.

Mots clés: ATP7A; Dysautonomia; Menkes disease; Occipital horn syndrome; X-linked distal spinal muscular atrophy-3

Domaines: Sciences du Vivant [q-bio]

Melanie Fradin, Alinoe Lavillaureix, Sylvie Jaillard, Chloe Quelin, Paul Sauleau, et al.. ATP7A mutation with occipital horns and distal motor neuropathy: A continuum. European Journal of Medical Genetics, 2020, 63 (12), pp.104087. ⟨10.1016/j.ejmg.2020.104087⟩. ⟨hal-03006935⟩