OTTAWA—Performing a muscle biopsy too early in patients with congenital myopathy may lead to a misdiagnosis, investigators have cautioned. Stanley Johnsen, MD, and John Bodensteiner, MD, recommended that a muscle biopsy in children with suspected congenital myopathy be deferred beyond infancy or later when clinically practical.

“The timing of the biopsy is more important in congenital myopathy than generally appreciated,” said Dr. Johnsen. “Our experience indicates that biopsies done very early in life may be particularly difficult, and a thoughtful delay may be useful.... There is no absolute precise time to do a muscle biopsy in assessment of congenital myopathy. A repeat muscle biopsy at a later date in those with fiber-type disproportion may reveal more specific pathology.” Dr. Johnsen is a Pediatric Neurologist at the Barrow Neurological Institute and Children’s Health Center, St. Joseph’s Hospital, Phoenix. The researchers made their presentation at the 33rd National Meeting of the Child Neurology Society.

Child neurologists frequently encounter children from the neonatal period and older who are hypotonic and weak. When muscle enzyme levels are normal, and appropriate DNA testing is negative, the possibility of a congenital myopathy is foremost. It is widely presumed that because a muscle disorder is congenital, histologic appearance remains unchanged throughout life and that age at muscle biopsy is immaterial. “The urgency for a diagnosis to accurately prognosticate and advise the family of genetic risk frequently compels immediate action, necessitating a muscle biopsy,” Dr. Johnsen said. However, nonspecific findings from a prematurely done biopsy leave diagnostic uncertainty, he noted.

THREE CASE SUMMARIES

Drs. Johnsen and Bodensteiner evaluated three patients whose initial biopsies were not diagnostic but whose subsequent biopsies were. In each case, the early biopsy had not revealed the full nature of the pathology, showing only nonspecific features. However, in all three cases a diagnosis was eventually established. All patients had weakness, minimal to no elevation of creatine kinase, and a myopathic electromyography when done.

One patient, a 13-year-old boy, had presented early in life with delayed walking. At age 2, a muscle biopsy revealed fiber-type disproportion, and his weakness persisted. At age 10, a repeat muscle biopsy demonstrated rod-body myopathy. He also has a sister with rod-body myopathy.

A second case involved a 6-year-old boy who had presented at birth with severe hypotonia and weakness involving his extremities and face and had required respiratory support. A muscle biopsy performed at six weeks revealed that he had severe fiber-type disproportion suggesting denervation. His clinical situation became stable, but severe weakness persisted, and he had very limited movement. A second muscle biopsy done at age 1 year revealed rod-body myopathy.

A second case involved a 6-year-old boy who had presented at birth with severe hypotonia and weakness involving his extremities and face and had required respiratory support. A muscle biopsy performed at six weeks revealed that he had severe fiber-type disproportion suggesting denervation. His clinical situation became stable, but severe weakness persisted, and he had very limited movement. A second muscle biopsy done at age 1 year revealed rod-body myopathy.

The third case was that of a 5-year-old girl who had hypotonia and weakness from infancy and who has not progressed. An initial biopsy performed at age 7 months revealed fiber-type disproportion. She was delayed in walking and persisted with weakness and hypotonia but showed some slight improvement with time. A second biopsy was done at age 3.5 because of her parents’ request for genetic counseling related to a desire to have additional children. The second biopsy demonstrated centronuclear myopathy.

VALUE IN REPETITION

Dr. Johnsen believes that these three cases indicate the value of a repeat muscle biopsy in circumstances in which initial reports had indicated nonspecific changes, particularly fiber-type disproportion. “This experience also reinforces the value of delay in obtaining a muscle biopsy in children with suspected congenital myopathy,” he stated. “In addition to the opportunity for greater muscle sample and reduced size of scar, it is clear from this report that maturation may facilitate the accuracy of the diagnostic process. We prefer to defer a muscle biopsy done for purposes of assessing congenital myopathy until the child is nearly 2 years of age. However, it is clear from these patients that there is no absolute age and that even at 2 years of age nonspecific pathology may be encountered.”

NR

—Colby Stong

Suggested Reading
Jeannet PY, Bassez G, Eymard B, et al. Clinical and histologic findings in autosomal centronuclear myopathy. Neurology. 2004;62:1484-1490.
Riggs JE, Bodensteiner JB, Schochet SS Jr. Congenital myopathies/dystrophies. Neurol Clin. 2003;21:779-794; v-vi.

Return to table of contents