(Nemaline rod myopathy, nemaline dystrophy ) 

Rare: 1/50.000 except for the Amish form where the prevalence is 1/500. In general, sporadic transmission (65%) but autosomal recessive and dominant forms exist. Ten genes are associated with this myopathy without any precise correlation between the genotype and the severity of the phenotype: 

At least 4 clinical presentations have been described:

-         severe congenital form (ACTA-1, NEB, KLHL 40, LMOD3): massive muscle involvement with lack of spontaneous motricity requiring assisted ventilation and gavage feeding; death usually occurs in the 1st year of life.

-         intermediate congenital form (NEB) (there is also a form known as the Amish nemaline myopathy: TNNT1): hypotonia and generalized muscle weakness that appear after a few months of life; important developmental retardation: neither walking nor seating are acquired; scoliosis and muscle contracture with early respiratory failure.

-         typical form (NEB, TMP2, KLHL41): onset at a variable age, diffuse muscle involvement with amyotrophy and marked muscle contractures, restrictive pulmonary syndrome, swallowing disorders and narrow facies with pro- or micrognathia, which can lead to intubation difficulties.

-         form beginning in childhood or adolescence (TPM3): late onset of muscle weakness which is generally proximal

Other rarer forms:

-         sporadic form starting in adulthood: quickly generalizing with death by cardiac involvement; approximately 50% of these late-onset forms are acquired and associated with a benign monoclonal  IgG gammopathy (MGUS acronym for Monoclonal Gammapathy of Undetermined Significance ) and respond partly to corticotherapy with or without azathioprine, even after a bone marrow transplantation.

-         asymptomatic form: rare, only found at muscle biopsy during familial screening.

-        a mostly cardiac form in cases related to a mutation the ACTA1 gene: dilated cardiomyopathy, congestive heart failure, ventricular rhythm disorders.

The CPK level is little or not elevated. Death is caused by progressive respiratory failure often aggravated by aspiration pneumonitis secondary to bulbar impairment.

In some cases, a mutation in the RYR1 (19q13.2) or NEB-KBTBD3 gene leads to the appearance of central "cores" and this variant is called core-rod myopathy (see central core disease).

An ACTA1 gene mutation can also cause the zebra bodies myopathy that is considered to be a variant of rod myopathy. Another variant is the cap myopathy where there is a rearrangement of the thin muscular filaments: it presents like a typical form of rod myopathy but the histological picture shows a "cap" in periphery of the muscle fibers. It is associated with mutations of ACTA1, TPM3 or TPM2 gene.

A mutation of the MYO18B gene (22q12.1) [MIM 616 549] leads to the combinaison of a rod myopathy, facial dysporphism and  Klippel-Feil syndrome (see this term).

The nemalin rod myopathy is due to an autosomal recessive transmission of the RYR3 gene (15q13-q14).

Rods are visible in optical or electron microscopy and correspond to cytoplasmic inclusions derived from proteins (actin, α-actinin) in the Z zone of the muscle fibers. 

Anesthetic implications: 

diagnosis to be kept in mind in case of delayed walking, rapid muscle weakness at exercising or association of dysarthria, contractures and scoliosis. Echocardiography: cardiomyopathy ? The patient sometimes benefits from an automatic internal cardiac defibrillator. No case of malignant hyperthermia associated with the different forms of rod myopathy has been published so far. However, in case of  RYR1 gene mutation or "core" disease, there is a risk of malignant hyperthermia. Risk of difficult intubation. Avoid succinylcholine as for any myopathy. Overnight non-invasive ventilation in case of severe respiratory failure. Muscle atrophy and swallowing disorders.

References : 

• Shenkman Z, Sheffer O, Erez I, Litmanovic I, Jedeikin R. Spinal anesthesia for gastrostomy in an infant with nemaline myopathy. Anesth Analg 2000; 91: 858-9.
• Heard SO, Kaplan RF. Neuromuscular blockade in a patient with nemaline myopathy. Anesthesiology 1983; 59: 588-90.
• Klingler W, Rueffert H, Lehmann-Horn F, Girard T, Hopkins PM. Core myopathies and risk of malignant hyperthermia. Anesth Analg 2009; 109: 1167-73.

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Updated: July 2021