Congenital immobility and stiffness related to biallelic ATAD1 variants

Roxane Bunod; Diane Doummar; Sandra Whalen; Boris Keren; Sandra Chantot-Bastaraud; Kim Maincent; Marie-Charlotte Villy; Michèle Mayer; Diana Rodriguez; Lydie Burglen; Pierre-Louis Léger; François Kieffer; Isabelle Martin; Delphine Héron; Julien Buratti; Arnaud Isapof; Alexandra Afenjar; Thierry Billette de Villemeur; Cyril Mignot

doi:10.1212/NXG.0000000000000520

Congenital immobility and stiffness related to biallelic ATAD1 variants

Neurol Genet. 2020 Sep 24;6(6):e520. doi: 10.1212/NXG.0000000000000520. eCollection 2020 Dec.

Authors

Roxane Bunod¹, Diane Doummar¹, Sandra Whalen¹, Boris Keren¹, Sandra Chantot-Bastaraud¹, Kim Maincent¹, Marie-Charlotte Villy¹, Michèle Mayer¹, Diana Rodriguez¹, Lydie Burglen¹, Pierre-Louis Léger¹, François Kieffer¹, Isabelle Martin¹, Delphine Héron¹, Julien Buratti¹, Arnaud Isapof¹, Alexandra Afenjar¹, Thierry Billette de Villemeur¹, Cyril Mignot¹

Affiliation

¹ Département de Génétique (R.B., S.W., B.K., S.C.-B., M.-C.V., L.B., D.H., J.B., A.A., C.M.), Hôpital Armand Trousseau & Groupe Hospitalier Pitié-Salpêtrière, and Unité de Neuropédiatrie et Pathologie du Développement (D.D., M.M., D.R., A.I., T.B.V.), Hôpital Armand Trousseau, AP-HP Sorbonne Université, Paris; Centre de Référence des Maladies Neurogénétiques (D.D., D.R.); Centre de Référence Anomalies du Développement et Syndromes Malformatifs (S.W., C.M.); Hôpital de Pédiatrie et de Rééducation (K.M.), Bullion; INSERM UMR 1141 (D.R.), Paris; Réanimation Néonatale et Pédiatrique (P.-L.L.), and Service de Néonatologie (F.K., I.M.), Hôpital Armand Trousseau, AP-HP Sorbonne Université, Paris; Centre de Référence Déficience Intellectuelles de Causes Rares (D.H., A.A., T.B.V., C.M.); and INSERM (C.M.), U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Université Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle Epinière, Paris, France.

Abstract

Objective: To delineate the phenotype associated with biallelic ATAD1 variants.

Methods: We describe 2 new patients with ATAD1-related disorder diagnosed by whole-exome sequencing and compare their phenotype to 6 previous patients.

Results: Patients 1 and 2 had a similar distinctive phenotype comprising congenital stiffness of limbs, absent spontaneous movements, weak sucking, and hypoventilation. Both had absent brainstem evoked auditory responses (BEARs). Patient 1 carried the homozygous p.(His357Argfs*15) variant in ATAD1. In the light of the finding in patient 1, a second reading of exome data for patient 2 revealed the novel homozygous p.(Gly128Val) variant.

Conclusions: Analysis of the phenotypes of these 2 patients and of the 6 previous cases showed that biallelic ATAD1 mutations are responsible for a unique congenital encephalopathy likely comprising absent BEAR, different from hyperekplexia and other conditions with neonatal hypertonia.