Ocular Dysmetria in a Patient with Charcot-Marie- Tooth Disease Michelle Lee, OD

A patient with the inherited neuropathy, Charcot-Marie-Tooth disease (CMT), presents with ocular dysmetria. Although abnormal ocular motility has not been reported in CMT patients, the absence of other etiologies indicates a possible ocular manifestation.

CASE HISTORY • Patient demographics: 74 year old Caucasian male • Chief complaint: no visual or ocular complaints • Ocular History o Mild OU o OU o OU • Medical history o Charcot-Marie-Tooth disease o Asthma o Hypercholesterolemia o Herpes zoster o Chronic lower back o Dermatitis o Obstructive sleep apnea • Medications o Albuterol o Gabapentin o Meloxicam o Mometasone furoate o Oxybutynin chloride o Simvastatin o Tamusolisn HCL o Aspirin o Vitamin D • Ocular medications: artificial tears prn OU • Family history: father and grandfather also with CMT

PERTINENT FINDINGS • Clinical o Mixed hypometric and hypermetric saccades with intermittent disconjugate movement o Trace restriction of lateral gaze and inferior temporal OS o OD o Borderline reduced contrast sensitivity OD, mildly reduced contrast sensitivity OS o Pertinent negatives: no evidence of light-near-dissociation, no signs of

1 of 4 • Physical o Abnormal gait • Lab studies o EMG consistent with positive family history of CMT • Radiology studies o MRI (04/13): no intracranial mass or acute infarcts seen, no evidence of cerebellar abnormality noted

DIFFERENTIAL DIAGNOSIS • Primary/leading – ocular dysmetria 2/2 CMT • Other o Cerebrovascular accident o Traumatic brain injury o o Amytrophic lateral sclerosis o Intracranial mass

DIAGNOSIS AND DISCUSSION • About Charles-Marie-Tooth disease o Inherited genetic neuropathy that affects peripheral motor and/or sensory nerves § Prevalence is estimated to be 1 in 2500 with symptoms presenting in the first two decades of life o Cause: gene mutations that can be inherited in an autosomal dominant, autosomal recessive, or x-linked pattern § Mutations affect myelin sheath, or less commonly, the axons leading to reduced nerve conduction • The most common mutation is a gene duplication in peripheral myelin protein 22 (PMP22) on chromosome 17 - a gene expressed mainly in Schwann cells and is involved in producing myelin • Less common mutation can occur in the gene MFN2, which causes an inability for mitochondria to travel along axons, resulting in clusters of mitochondria that block synaptic function § Several CMT phenotypes have been identified with over 70 distinct genes involved • CMT1: demyelinating condition, more common in Western countries o Conduction velocity < 38 m/s o Autosomal dominant • CMT2: axonal condition o Conduction velocity > 38 m/s o Autosomal dominant • CMT 3: early onset • CMT4: usually demyelinating o Autosomal recessive • CMTX: usually demyelinating o X-linked

2 of 4 o Symptoms: § Weak handgrip and difficulty with fine motor skills § Foot deformities like foot drop, or inability to lift the front part of the foot § Abnormal gait § Difficulty with balance and sensory ataxia from proprioceptive sensory loss and vestibular impairment o Diagnostic testing § History and physical examination § Electromyogram § Nerve conduction studies § Genetic testing • Ocular manifestations o abnormalities have been reported in 17% of patients with CMT, especially CMT2 § Tonic § Argyll-Robertson § Horner’s § o Optic atrophy o o o Cataracts o Case report of bilateral vitritis o Subclinical optic neuropathy based on reduced contrast sensitivity and visual • Unique features o There are a limited numbers of case reports that highlight the ocular manifestations of CMT and few, if any, report abnormalities of ocular motility. The absence of other systemic causes, as well as normal MRI in this patient, suggests that ocular dysmetria is possibly associated with CMT.

TREATMENT, MANAGEMENT • Treatment and response to treatment o Ocular findings can generally be observed and other etiologies ruled out. For this patient, a neurology follow-up with gait evaluation was recommended by the primary care provider o One study has suggested that “rehearsal by eye movement” can improve visuomotor function and reduced saccadic dysmetria in patients with cerebellar conditions. § Rehearsals involved making saccadic eye movements to a series of foot targets before walking. Given the absence of cerebellar lesions in this patient, the same rehearsals may not be beneficial. o Multi-disciplinary management of patients with CMT should involve neurology, orthopedic surgeons, and occupation or physical therapy with consideration for psychiatry to address a patient’s quality of life o Studies have shown that diabetes mellitus can exacerbate peripheral neuropathy and patients should undergo routine diabetes screening. o Genetic counseling may be considered to evaluate the risk for future generations

3 of 4 CONCLUSION • Current literature about the ocular manifestations of CMT is limited to a small sample of case reports, none of which have identified ocular dysmetria as a likely association. This report highlights an additional way in which a demyelinating condition may manifest itself ocularly. • Patients identified as having CMT should be managed by a multi-disciplinary approach and appropriate referrals should be made, including routine screenings for diabetes. • Should a patient present with CMT, optometrists should be aware of possible ocular manifestations and perform appropriate testing.

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