Nosological delineation of congenital ocular motor apraxia type Cogan: an observational study

Sarah Wente,
Simone Schröder,
Johannes Buckard,
Hans-Martin Büttel,
Florian von Deimling,
Wilfried Diener,
Martin Häussler,
Susanne Hübschle,
Silvia Kinder,
Gerhard Kurlemann,
Christoph Kretzschmar,
Michael Lingen,
Wiebke Maroske,
Dirk Mundt,
Iciar Sánchez-Albisua,
Jürgen Seeger,
Sandra P. Toelle,
Eugen Boltshauser and
Knut BrockmannEmail author View ORCID ID profile

Orphanet Journal of Rare Diseases201611:104

DOI: 10.1186/s13023-016-0486-z

Received: 8 April 2016

Accepted: 14 July 2016

Published: 29 July 2016

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.