I have a habit of perseverating on patients that present as clinical oddities.

Patient whose clinical diagnostic puzzles may not be particularly pathological or emergent, just out of the box, keeping me interested. One particular patient, I see every year, and every year I interrogate him about his health history. Every visit I expect him to tell me he is diabetic. He had nuclear sclerotic cataracts at 40 and had surgery at 45. He is not diabetic, no history of steroid use, no medical illnesses reported and he grew up in the Midwest, not Florida. Every year I try to explain his early cataracts, and can’t.

The majority of early-onset cataracts are associated with traumatic injury, ocular surgery, diabetes, use of steroidal medications, or a family history of early cataracts. This patient had none of these. He has not taken amniodarone or other meds associated with early onset cataracts. There was no history of congenital infection such as rubella, toxoplasmosis, herpes simplex or cytomgegalovirus. There was no history of uveitis, arthritis, ocular infection, and he did not suffer from any metabolic disorders. His only lab anomaly was chronically low levels of vitamin D. 

This year I got a lucky break on a possible etiology. He reported numbness in his feet and reported the doctor thought he may have peripheral neuropathy. Peripheral neuropathy and cataracts – my brain started to whir. The neurologist wanted him to get tested for Charcot Marie Tooth, one of the most common forms of inherited peripheral neuropathy. It is also called hereditary motor and sensory neuropathy (HMSN) or peroneal muscular atrophy. While it has multiple forms, some subtypes are related to cataracts.

Symptoms are related to problems with both sensory and motor nerves. The muscles of the foot and lower leg become weak, resulting in high arches, hammertoes, a foot drop, and a high-stepped gait. There is typically decreased or absence of tendon reflexes as well. Patients may report falls and tingling or numbness in their feet. Later in the disease, the hands may also be affected, causing problems with fine motor skills. Pain is frequently present in some form, yet there is no consensus in the literature regarding the etiology of pain.   

Symptoms typically present in adolescence, but this is variable and symptoms may not develop until adulthood. It is not life-threatening in most cases and rarely results in respiratory muscle weakness. 

The prevalence of CMT is approximately 1 in 2500. Inheritance is variable and may be autosomal dominant, recessive or X-linked. Family histories are required, but genetic testing is currently available. Genetic testing is expensive however, which may prohibit patients from having this testing performed. The spectrum of genetic mutation is large, spanning more than 70 genes.,

CMT disease diagnosis is divided into two classes according to where the dysfunction occurs in the peripheral nerves. In CMT type 1, the peripheral nerves lose their myelin sheaths, disrupting conduction. In CMT type 2, a diminished axonal response occurs due to a defect within the axons themselves. CMT type 2 is less common than type 1 and may be further separated into at least six subtypes resulting from specific genetic defects. Genetic testing may be beneficial if there is doubt about the subtype, or genetic counseling is preferred. It does not directly impact treatment, however.

Ophthalmic manifestation includes cataracts, optic neuropathy, and vitritis but ocular manifestations vary with subtype. Optic atrophy, changes in RNFL and GCC have been reported.

Corneal nerves have also been studied in CMT patients. Corneal sensitivity and nerve fiber density were significantly reduced in CMT1A patients compared with controls.

In addition to being familiar with this disorder’s ocular manifestations, it is also important to know that the disease can cause issues with general anesthesia. The need for orthopedic and cataract surgery requires anesthesia. Thankfully, the sedation required for phacoemulsification is less than that of orthopedic surgeries, but it is an important fact to discuss with the ophthalmologist and anesthesiologist. 

Anesthetic management in CMT patients includes prevention and prompt treatment of rare but potential complications including malignant hyperthermia and respiratory depression.  Awareness of prolonged responses to neuromuscular blocking drugs and toxicity caused by inappropriate doses in cases of severe muscle wasting, and avoidance of a medication-induced exacerbation of neuropathy. Shorter-acting drugs including propofol and desflurane are less likely to depress breathing. Due to nerve-damaging nature of CMT, anesthesiologists fear possible exacerbation of the disease by different classes of drugs that act on these nerves in regional anesthesia. Since denervation is a potent predisposing factor for potassium release after exposure to succinylcholine (SCH)12, its use is cautioned in these patients. Moreover, the response to non-depolarizing neuromuscular blocking drugs is variable in patients with CMTD and their effects may be prolonged.9

If presented with a patient with early onset cataracts, remember CMT if the patient has no history of the common health problems associated with cataracts. Discuss any signs of peripheral neuropathy with the patient, and consider referral to neurology prior to or concurrent with ophthalmology referral. Alert the surgeon and anesthesiologist to a CMT diagnosis when referring for surgery. 

  1. Charcot-Marie-Tooth Disease Fact Sheet.  National Institute of Neurological Disorders and Stroke. https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Charcot-Marie-Tooth-Disease-Fact-Sheet. Published 3/2018. Accessed June 24, 2018.
  2. Baets J, De Jonghe P, Timmerman V. Recent advances in Charcot-Marie-Tooth disease.  Curr Opin Neurol. 2014 Oct;27(5):532-40.
  3. Jani-Acsadi A, Ounpuu S, Pierz K, Acsadi G. Pediatric Charcot-Marie-Tooth disease. Pediatr Clin North Am. 2015 Jun;62(3):767-86.
  4. Learning About Charcot-Marie-Tooth Disease.  National Human Genome Society Research Institute.  https://www.genome.gov/11009201/learning-about-charcotmarietooth-disease/.  Accessed 7/10/2018.
  5. Anaya-Pava EJ, Cárdenas-Hernández RI.   Charcot-Marie-Tooth disease and bilateral vitritis.   Arch Soc Esp Oftalmol. 2015 Apr;90(4):185-9.
  6. Botsford B, Vuong LN, Hedges TR III, Mendoza-Santiesteban CE.  Characterization of Charcot-Marie-Tooth optic neuropathy.  J Neurol. 2017 Dec;264(12):2431-2435.
  7. Tavakoli M1, Marshall A, Banka S, Petropoulos IN, Fadavi H, Kingston H, Malik RA.  Corneal confocal microscopy detects small-fiber neuropathy in Charcot-Marie-Tooth disease type 1A patients.  Muscle Nerve. 2012 Nov;46(5):698-704.
  8. JFAntognini. Anesthesia and the CMT Patient.  http://cmt.freeservers.com/anesthesia_and_the_cmt_patient.htm.
  9. Khalid R, Alzaben, Omar Q. Samarah, Salameh S. Obeidat*, Oday HAlhouli Murad Al Kharabsheh.  Anesthesia for Charcot-Marie-Tooth Disease:   A Case Report.   M.E.J. Anesth 2016, 23 (5), 587-590.