title: Nosological delineation of congenital ocular motor apraxia type Cogan: an observational study.
abstract: The nosological assignment of congenital ocular motor apraxia type Cogan (COMA) is still controversial. While regarded as a distinct entity by some authorities including the Online Mendelian Inheritance in Man catalog of genetic disorders, others consider COMA merely a clinical symptom.
  
  
  
  We performed a retrospective multicenter data collection study with re-evaluation of clinical and neuroimaging data of 21 previously unreported patients (8 female, 13 male, ages ranging from 2 to 24 years) diagnosed as having COMA.
  
  
  
  Ocular motor apraxia (OMA) was recognized during the first year of life and confined to horizontal pursuit in all patients. OMA attenuated over the years in most cases, regressed completely in two siblings, and persisted unimproved in one individual. Accompanying clinical features included early onset ataxia in most patients and cognitive impairment with learning disability (n = 6) or intellectual disability (n = 4). Re-evaluation of MRI data sets revealed a hitherto unrecognized molar tooth sign diagnostic for Joubert syndrome in 11 patients, neuroimaging features of Poretti-Boltshauser syndrome in one case and cerebral malformation suspicious of a tubulinopathy in another subject. In the remainder, MRI showed vermian hypo-/dysplasia in 4 and no abnormalities in another 4 patients. There was a strong trend to more severe cognitive impairment in patients with Joubert syndrome compared to those with inconclusive MRI, but otherwise no significant difference in clinical phenotypes between these two groups.
  
  
  
  Systematical renewed analysis of neuroimaging data resulted in a diagnostic reappraisal in the majority of patients with early-onset OMA in the cohort reported here. This finding poses a further challenge to the notion of COMA constituting a separate entity and underlines the need for an expert assessment of neuroimaging in children with COMA, especially if they show cognitive impairment.
authors.affiliation: Interdisciplinary Pediatric Center for Children with Developmental Disabilities and Severe Chronic Disorders, Department of Pediatrics and Adolescent Medicine, University Medical Center, Robert Koch Str. 40, 37075, Göttingen, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Wente
authors.affiliation: Interdisciplinary Pediatric Center for Children with Developmental Disabilities and Severe Chronic Disorders, Department of Pediatrics and Adolescent Medicine, University Medical Center, Robert Koch Str. 40, 37075, Göttingen, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Schröder
authors.affiliation: Sozialpädiatrisches Zentrum, Evangelisches Krankenhaus, Düsseldorf, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Buckard
authors.affiliation: Sozialpädiatrisches Zentrum, SLK-Kliniken, Heilbronn, Germany.
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Büttel
authors.affiliation: Sozialpädiatrisches Zentrum, Coburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: von Deimling
authors.affiliation: Pediatric Practice, Offenburg, Germany.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Diener
authors.affiliation: Sozialpädiatrisches Zentrum, University Medical Center, Würzburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Häussler
authors.affiliation: Pediatric Practice, Mühlacker, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Hübschle
authors.affiliation: Sozialpädiatrisches Zentrum, University Medical Center, Dresden, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Kinder
authors.affiliation: Department of Pediatric Neurology, University Children's Hospital, Münster, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Kurlemann
authors.affiliation: Sozialpädiatrisches Zentrum, Städtisches Klinikum Dresden-Neustadt, Dresden, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kretzschmar
authors.affiliation: Interdisciplinary Pediatric Center for Children with Developmental Disabilities and Severe Chronic Disorders, Department of Pediatrics and Adolescent Medicine, University Medical Center, Robert Koch Str. 40, 37075, Göttingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Lingen
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Euregio-Klinik Grafschaft Bentheim Holding GmbH, Nordhorn, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Maroske
authors.affiliation: Sozialpädiatrisches Zentrum, St. Marien-Hospital, Düren, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Mundt
authors.affiliation: Department of Pediatric Neurology, University Children's Hospital, Tübingen, Germany.
authors.forename: Iciar
authors.initials: I
authors.lastname: Sánchez-Albisua
authors.affiliation: Sozialpädiatrisches Zentrum Frankfurt Mitte, Frankfurt am Main, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Seeger
authors.affiliation: Department of Pediatric Neurology, University Children's Hospital, Zurich, Switzerland.
authors.forename: Sandra P
authors.initials: SP
authors.lastname: Toelle
authors.affiliation: Department of Pediatric Neurology, University Children's Hospital, Zurich, Switzerland.
authors.forename: Eugen
authors.initials: E
authors.lastname: Boltshauser
authors.affiliation: Interdisciplinary Pediatric Center for Children with Developmental Disabilities and Severe Chronic Disorders, Department of Pediatrics and Adolescent Medicine, University Medical Center, Robert Koch Str. 40, 37075, Göttingen, Germany. kbrock@med.uni-goettingen.de.
authors.forename: Knut
authors.identifier: 0000-0001-6823-9091
authors.initials: K
authors.lastname: Brockmann
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000473:pathology; D000293:Adolescent; D000328:Adult; D001072:Apraxias / Q000151:congenital* / Q000175:diagnosis / Q000473:pathology; D002531:Cerebellum / Q000002:abnormalities / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D055952:Cogan Syndrome / Q000175:diagnosis* / Q000473:pathology; D005124:Eye Abnormalities / Q000175:diagnosis / Q000473:pathology; D005260:Female; D006801:Humans; D052177:Kidney Diseases, Cystic / Q000175:diagnosis / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D059906:Neuroimaging; D012160:Retina / Q000002:abnormalities / Q000473:pathology; D012189:Retrospective Studies; D055815:Young Adult
keywords: Congenital ocular motor apraxia; Joubert syndrome; Molar tooth sign