Neurological outcome in WDR62 primary microcephaly.

Cell Cycle Proteins; Nerve Tissue Proteins; WDR62 protein, human; Adolescent; Ataxia; Child; Child, Preschool; Female; Humans; Male; Young Adult; Cell Cycle Proteins/genetics; Intellectual Disability/diagnosis; Intellectual Disability/genetics; Microcephaly/diagnosis; Microcephaly/genetics; Nerve Tissue Proteins/genetics; Intellectual Disability; Microcephaly; Pediatrics, Perinatology and Child Health; Developmental Neuroscience; Neurology (clinical)

Abstract :

[en] AIM: To characterize the cortical structure, developmental, and cognitive profiles of patients with WD repeat domain 62 (WDR62)-related primary microcephaly. METHOD: In this observational study, we describe the developmental, neurological, cognitive, and brain imaging characteristics of 17 patients (six males, 11 females; mean age 12y 3mo standard deviation [SD] 5y 8mo, range 5y-24y 6mo) and identify 14 new variants of WDR62. We similarly analyse the phenotypes and genotypes of the 59 previously reported families. RESULTS: Brain malformations, including pachygyria, neuronal heterotopia, schizencephaly, and microlissencephaly, were present in 11 out of 15 patients. The mean full-scale IQ of the 11 assessed patients was 51.8 (standard deviation [SD] 12.6, range 40-70). Intellectual disability was severe in four patients, moderate in four, and mild in three. Scores on the Vineland Adaptive Behavior Scales obtained from 10 patients were low for communication and motor skills (mean 38.29, SD 7.74, and 37.71, SD 5.74 respectively). The socialization score was higher (mean 47.14, SD 12.39). We found a significant difference between scores for communication and daily living skills (mean 54.43, SD 11.6; p=0.001, one-way analysis of variance). One patient displayed progressive ataxia. INTERPRETATION: WDR62-related cognitive consequences may be less severe than expected because 3 out of 11 of the assessed patients had only mild intellectual disability and relatively preserved abilities of autonomy in daily life. We identified progressive ataxia in the second decade of life in one patient, which should encourage clinicians to follow up patients in the long term.

Disciplines :

Neurology
Pediatrics

Author, co-author :

Ruaud, Lyse ; Département de Génétique, UMR 1141 NEURODIDEROT, INSERM, APHP, Hôpital Universitaire Robert Debré, Université de Paris, Paris, France

Drunat, Séverine ; Département de Génétique, UMR 1141 NEURODIDEROT, INSERM, APHP, Hôpital Universitaire Robert Debré, Université de Paris, Paris, France

Elmaleh-Bergès, Monique ; Service d'Imagerie Pédiatrique, APHP, Hôpital Universitaire Robert Debré, Paris, France

Ernault, Anais; Département de Génétique, APHP, Hôpital Universitaire Robert Debré, Paris, France

Guilmin Crepon, Sophie ; Unité d'Epidémiologie Clinique, APHP, Hôpital Universitaire Robert Debré, Paris, France

MCPH Consortium

El Ghouzzi, Vincent ; UMR 1141 NEURODIDEROT, INSERM, Université de Paris, Paris, France

Auvin, Stéphane ; Service de Neurologie Pédiatrique, UMR 1141 NEURODIDEROT, INSERM, APHP, Hôpital Universitaire Robert Debré, Université de Paris, Paris, France ; Institut universitaire de France (IUF), Paris, France

Verloes, Alain ; Université de Liège - ULiège > Département des sciences précliniques BP > GIGA-R : Génétique humaine ; Département de Génétique, UMR 1141 NEURODIDEROT, INSERM, APHP, Hôpital Universitaire Robert Debré, Université de Paris, Paris, France

Passemard, Sandrine ; Service de Neurologie Pédiatrique, UMR 1141 NEURODIDEROT, INSERM, APHP, Hôpital Universitaire Robert Debré, Université de Paris, Paris, France

Servais, Laurent ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pédiatrie ; MCPH Consortium

VAESSEN, Sandrine ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pédiatrie ; MCPH Consortium

Language :

English

Title :

Neurological outcome in WDR62 primary microcephaly.

Publication date :

April 2022

Journal title :

Developmental Medicine and Child Neurology

ISSN :

0012-1622

eISSN :

1469-8749

Publisher :

John Wiley and Sons Inc, England

Volume :

Issue :

Pages :

509-517

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://onlinelibrary.wiley.com/doi/pdf/10.1111/dmcn.15060

Funders :

ANR - Agence Nationale de la Recherche

Funding text :

The members of the MCPH consortium are as follows: Lionel Van Maldergem, Camille Engel, Cecilia Altuzarra, Charlie Lamidieu, Allan Bayat, Stéphanie Moortgat, Karine Pelc, Isabelle Maystadt, Marc Abramowicz, Isabelle Pirson, Sarah Duerinckx, Nino Rostomashvili, Christiane Zweier, Rami Abou Jamra, Imke Lorenz, Damien Haye, Khaoula Zaafrane‐Khachnaoui, Sandrine Vaessen, Yline Capri, Laurent Servais, Emilio Di Maria, Jürgen Kohlhase, Thomas Bast, Najoua Miladi, and Selma Dali. We thank all patients and their families, the CIC team (CIC 1426, INSERM) at Robert Debré Hospital in Paris who organized the families’ visits and ensured the implementation of the clinical research protocol and coordination between collaborators. We also thank the MCPH consortium for collecting and sharing data and, during the COVID‐19 critical period, for having organized the neuropsychological assessments of their patients. Several authors of this publication are members of the European Reference Network for Developmental Anomalies and Intellectual Disability. This study was supported by the Microfanc project (number NCT01565005) and European e‐Rare Euromicroproject (ANR‐13‐RARE‐0007‐01). The authors have stated that they had no interests that might be perceived as posing conflict or bias.The members of the MCPH consortium are as follows: Lionel Van Maldergem, Camille Engel, Cecilia Altuzarra, Charlie Lamidieu, Allan Bayat, Stéphanie Moortgat, Karine Pelc, Isabelle Maystadt, Marc Abramowicz, Isabelle Pirson, Sarah Duerinckx, Nino Rostomashvili, Christiane Zweier, Rami Abou Jamra, Imke Lorenz, Damien Haye, Khaoula Zaafrane-Khachnaoui, Sandrine Vaessen, Yline Capri, Laurent Servais, Emilio Di Maria, Jürgen Kohlhase, Thomas Bast, Najoua Miladi, and Selma Dali. We thank all patients and their families, the CIC team (CIC 1426, INSERM) at Robert Debré Hospital in Paris who organized the families’ visits and ensured the implementation of the clinical research protocol and coordination between collaborators. We also thank the MCPH consortium for collecting and sharing data and, during the COVID-19 critical period, for having organized the neuropsychological assessments of their patients. Several authors of this publication are members of the European Reference Network for Developmental Anomalies and Intellectual Disability. This study was supported by the Microfanc project (number NCT01565005) and European e-Rare Euromicroproject (ANR-13-RARE-0007-01). The authors have stated that they had no interests that might be perceived as posing conflict or bias.

Available on ORBi :

since 14 February 2023

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