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PDE10A mutation in two sisters with a hyperkinetic movement disorder - Response to levodopa

2019; Elsevier BV; Volume: 63; Linguagem: Inglês

10.1016/j.parkreldis.2019.02.007

1873-5126

Cordula Knopp, Martin Häusler, Boris Müller, Reinhild Damen, Arzu Stoppe, Michael Mull, Miriam Elbracht, Ingo Kurth, Matthias Begemann,

Autism Spectrum Disorder Research

PDE10A (OMIM *610652, #616921, #616922) encodes phosphodiesterase 10A, which regulates the intracellular concentration of cAMP and cGMP in medium spiny neurons (MSNs) of the corpus striatum (for review [ [1] Threlfell S. West A.R. Review: modulation of striatal neuron activity by cyclic nucleotide signaling and phosphodiesterase inhibition. Basal Ganglia. 2013; 3: 137-146 Crossref PubMed Scopus (44) Google Scholar ]). Both recessive [ [2] Diggle C.P. Sukoff Rizzo S.J. Popiolek M. Hinttala R. Schülke J.P. Kurian M.A. Carr I.M. Markham A.F. Bonthron D.T. Watson C. Sharif S.M. Reinhart V. James L.C. Vanase-Frawley M.A. Charych E. Allen M. Harms J. Schmidt C.J. Ng J. Pysden K. Strick C. Vieira P. Mankinen K. Kokkonen H. Kallioinen M. Sormunen R. Rinne J.O. Johansson J. Alakurtti K. Huilaja L. Hurskainen T. Tasanen K. Anttila E. Marques T.R. Howes O. Politis M. Fahiminiya S. Nguyen K.Q. Majewski J. Uusimaa J. Sheridan E. Brandon N.J. Biallelic mutations in PDE10A lead to loss of striatal PDE10A and a hyperkinetic movement disorder with onset in infancy. Am. J. Hum. Genet. 2016; 98: 735-743 Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar ] and dominant mutations [ [3] Mencacci N.E. Kamsteeg E.J. Nakashima K. R'Bibo L. Lynch D.S. Balint B. Willemsen M.A. Adams M.E. Wiethoff S. Suzuki K. Davies C.H. Ng J. Meyer E. Veneziano L. Giunti P. Hughes D. Raymond F.L. Carecchio M. Zorzi G. Nardocci N. Barzaghi C. Garavaglia B. Salpietro V. Hardy J. Pittman A.M. Houlden H. Kurian M.A. Kimura H. Vissers L.E. Wood N.W. Bhatia K.P. De novo mutations in PDE10A cause childhood-onset chorea with bilateral striatal lesions. Am. J. Hum. Genet. 2016; 98: 763-771 Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar ] in PDE10A have recently been found to cause an infantile/childhood-onset hyperkinetic movement disorder. In comparison to patients with dominant PDE10A mutations, the eight reported patients of two families with homozygous PDE10A mutations showed no striatal lesions on MRI but a more severe clinical presentation with a generalized hyperkinetic movement disorder characterized by limb and orofacial dyskinesia within the first six months of life, and mild cognitive impairment in some patients [ [2] Diggle C.P. Sukoff Rizzo S.J. Popiolek M. Hinttala R. Schülke J.P. Kurian M.A. Carr I.M. Markham A.F. Bonthron D.T. Watson C. Sharif S.M. Reinhart V. James L.C. Vanase-Frawley M.A. Charych E. Allen M. Harms J. Schmidt C.J. Ng J. Pysden K. Strick C. Vieira P. Mankinen K. Kokkonen H. Kallioinen M. Sormunen R. Rinne J.O. Johansson J. Alakurtti K. Huilaja L. Hurskainen T. Tasanen K. Anttila E. Marques T.R. Howes O. Politis M. Fahiminiya S. Nguyen K.Q. Majewski J. Uusimaa J. Sheridan E. Brandon N.J. Biallelic mutations in PDE10A lead to loss of striatal PDE10A and a hyperkinetic movement disorder with onset in infancy. Am. J. Hum. Genet. 2016; 98: 735-743 Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar ]. Here we describe two sisters with a novel homozygous PDE10A mutation, presenting with a generalized hyperkinetic movement disorder. This is the first report showing improved clinical outcome of levodopa therapy.