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

Abstract

BackgroundThe 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.MethodsWe 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.ResultsOcular 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.ConclusionsSystematical 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-016-0486-z) contains supplementary material, which is available to authorized users.

De novo ITPR1 variants are a recurrent cause of early-onset ataxia, acting via loss of channel function

“…Moreover, our phenotypic results show that the oculomotor presentation of ITPR1 can also encompass congenital oculomotor apraxia, elaborating on a previous report of de novo ITPR1 patients [3]. Our findings thus extend the genetic basis of the well-recognized syndrome of "congenital oculomotor apraxia" (COMA [9]; OMIM #257550), where the genetic background beyond Joubert syndrome had still remained largely elusive [9].…”

“…In contrast, 4/7 patients showed strabismus (Table 2), suggesting that it is a frequent feature of de novo ITPR1 ataxia. One patient (P2) also revealed congenital horizontal oculomotor apraxia (COMA [9]), i.e., slowed initiation and performance of horizontal saccades. The oculomotor apraxia slowly ameliorated throughout the following disease course, but still precludes her from obtaining driving license at her current age of 18 years.…”

Homozygosity for the c.428delG variant in KIAA0586 in a healthy individual: implications for molecular testing in patients with Joubert syndrome

“…Clinical and neuroimaging details were described previously (patients #8 and #9 in Ref. 11). In brief, both siblings presented in their first year of life with impaired fixation, poor visual pursuit, muscular hypotonia and motor developmental delay.…”

Nephronophthise und assoziierte Ziliopathien

“…50 % der COMA-Patienten radiologisch ein "molar tooth sign" aufwiesen und folglich als Joubert-Syndrom reklassifiziert werden müssten. Darüber hinaus sind COMA-spezifische Genmutationen nicht bekannt; beschriebene Mutationen finden sich in anderweitig bekannten NPH-RC-Genen (NPHP1, 4,6,8,11) [13].…”