speech delay

Cerebellar Atrophy, Visual Impairment, and Psychomotor Retardation

Clinical Characteristics
Ocular Features: 

Patients usually have deep-set eyes.  Cortical visual impairment has been described in one patient but optic atrophy has been seen in another.  The VEP and ERG are described as 'abnormal'.  Strabismus, hyperopia, and myopia are sometimes seen.

Systemic Features: 

Progressive microcephaly is often noted.  Truncal hypotonia and scoliosis may be present while muscle tone is increased in the extremities in the presence of diminished deep tendon reflexes in other patients.  Dystonic posturing occurs in some families.  Gingival hyperplasia is a common feature and retrognathia is often present.

Brain imaging reveals progressive cerebellar atrophy and a foreshortened corpus callosum in all families.  Various degrees of cerebral atrophy have been identified while intellectual disability may be marked.  Speech delay is common.

Genetics

This is an autosomal recessive condition associated with homozygous mutations in the EMC1 gene (1p36.13).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatnent has been reported.

References
Article Title: 

Monoallelic and Biallelic Variants in EMC1 Identified in Individuals with Global Developmental Delay, Hypotonia, Scoliosis, and Cerebellar Atrophy

Harel T, Yesil G, Bayram Y, Coban-Akdemir Z, Charng WL, Karaca E, Al Asmari A, Eldomery MK, Hunter JV, Jhangiani SN, Rosenfeld JA, Pehlivan D, El-Hattab AW, Saleh MA, LeDuc CA, Muzny D, Boerwinkle E; Baylor-Hopkins Center for Mendelian Genomics, Gibbs RA, Chung WK, Yang Y, Belmont JW, Lupski JR. Monoallelic and Biallelic Variants in EMC1 Identified in Individuals with Global Developmental Delay, Hypotonia, Scoliosis, and Cerebellar Atrophy. Am J Hum Genet. 2016 Mar 3;98(3):562-70.

PubMed ID: 
26942288

Oculomotor Apraxia

Clinical Characteristics
Ocular Features: 

This is a disorder of impaired smooth ocular pursuit movements.  Voluntary horizontal eye movements are absent or defective while vertical gaze and random eye movements are usually retained.  Patients learn early to compensate by sharply turning the head in a jerky, thrusting fashion.  The head turn often overshoots because the eyes tend to deviate in the opposite direction as a result of the vestibular reflex.  Blinking is also sometimes employed to initiate eye movements.  The condition is likely congenital in onset but it is not progressive.  In fact, the ability to look from side to side improves in at least some patients.

Systemic Features: 

The small number of reported patients has limited description of the full phenotype but this seems to be a generalized neurological disorder.  Patients have been reported with global developmental delay, hypotonia, cognitive delays, ataxia/clumsiness, and speech difficulties.  Neuroimaging may reveal abnormalities in various brain stuctures including the cerebellum, cerebrum, vermis, and corpus callosum in 40% of patients.       

Genetics

The genetics of isolated oculomotor apraxia is unknown since no responsible mutation has been identified.  However, familial cases are known, including twins and sibling offspring of consanguineous matings, as well as multigenerational cases.  This condition may be genetically heterogeneous since autosomal recessive and autosomal dominant transmission patterns seem equally likely.  It may also be possible that the Cogan-type oculomotor apraxia is not a isolated entity but simply an associated sign as part of more generalized neurological disease.

Oculomotor apraxia may also be seen in ataxia-telangiectasia (208900), ataxia with oculomotor apraxia 1 (208920), ataxia with oculomotor apraxia 2 (602600) and in Gaucher disease (203800).  It may be the presenting sign in the latter disease.  

Pedigree: 
Autosomal dominant
Autosomal recessive
Treatment
Treatment Options: 

No treatment is known.

References
Article Title: 

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

Wente S, Schroder S, Buckard J, Buttel HM, von Deimling F, Diener W, Haussler M, Hubschle S, Kinder S, Kurlemann G, Kretzschmar C, Lingen M, Maroske W, Mundt D, Sanchez-Albisua I, Seeger J, Toelle SP, Boltshauser E, Brockmann K. Nosological delineation of congenital ocular motor apraxia type Cogan: an observational study. Orphanet J Rare Dis. 2016 Jul 29;11(1):104. doi: 10.1186/s13023-016-0486-z.

PubMed ID: 
27473762
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