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Agenesis of Pectoralis Major Muscle in Late-Onset GFPT1-Related Congenital Myasthenic Syndrome: A Case Report
Erika K Williams1, Cristina Shea1, Paloma Gonzalez-Perez1
1From the Department of Neurology (E.K.W., C.S., P.G.-P.), Massachusetts General Hospital; and Department of Neurology (E.K.W., C.S.), Brigham Women's Hospital, Harvard Medical School, Boston, MA.
Insights
This study identifies Poland syndrome as a potential symptom of GFPT1-related congenital myasthenia syndrome (CMS). Early diagnosis and treatment with pyridostigmine can significantly improve muscle strength in affected individuals.
Area of Science:
- Neurology
- Genetics
- Rare Diseases
Background:
- Congenital myasthenia syndrome (CMS) is a group of rare inherited disorders affecting neuromuscular transmission.
- Glutamine-fructose-6-phosphate transaminase 1 (GFPT1) gene mutations are a known cause of CMS.
- The phenotypic spectrum of GFPT1-related CMS is still being defined.
Purpose of the Study:
- To expand the known clinical manifestations of GFPT1-related congenital myasthenia syndrome (CMS).
- To investigate a patient with unexplained muscle weakness and pectoralis major muscle agenesis.
Main Methods:
- Clinical examination and electrophysiological testing (repetitive nerve stimulation) were performed.
- Genetic testing identified pathogenic variants in the GFPT1 gene.
- Treatment response to pyridostigmine was assessed.
Main Results:
- A patient with progressive muscle weakness and pectoralis major muscle agenesis (Poland syndrome) was diagnosed with GFPT1-related CMS.
- Genetic analysis revealed two likely pathogenic variants in the GFPT1 gene.
- The patient showed significant improvement in muscle strength after pyridostigmine treatment.
Conclusions:
- Pectoralis major muscle agenesis (Poland syndrome) can be a presenting feature of GFPT1-related CMS.
- Genetic testing for GFPT1 variants is crucial for diagnosing atypical CMS cases.
- Early diagnosis and symptomatic treatment can improve outcomes for patients with GFPT1-related CMS.
Objectives:
The objective of this study was to expand the phenotypic spectrum of glutamine-fructose-6-phosphate transaminase 1 (GFPT1)-related congenital myasthenia syndrome (CMS).
Methods:
A 61-year-old man with agenesis of the left pectoralis major muscle presented with progressive muscle weakness for a decade that transiently improved after exertion.
Results:
His examination revealed proximal and distal muscle weakness in upper extremities and proximal muscle weakness in lower extremities. Muscle enzymes were elevated. An electromyogram revealed a myopathic pattern; however, a muscle biopsy of deltoid muscle and genetic testing for limb-girdle muscular dystrophies were nondiagnostic. A 3-Hz repetitive nerve stimulation of the spinal accessory nerve recording from trapezius muscle demonstrated a >20% drop in amplitude of the 5th compound motor action potential relative to 1st at both baseline and after 45-second exercise. Acetylcholine receptor binding, lipoprotein-related protein 4, muscle-specific kinase, and voltage-gated calcium channel P/Q antibodies were negative. Genetic testing targeting CMS revealed 2 likely pathogenic variants within GFPT1: novel c.7+2T>G (intron 1) that was predicted to result in a null allele and known c*22 C>A (exon 19) associated with reduced GFPT1 expression. His muscle strength dramatically improved after pyridostigmine initiation.
Discussion:
In addition to other reported neurodevelopmental abnormalities, pectoralis major muscle agenesis (or Poland syndrome) may be a clinical manifestation of GFPT1-related CMS.
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