Lamin A/C Mutations Do Not Cause Left Ventricular Hypertrabeculation/Noncompaction
To the Editor:
We read the article by Parent and colleagues1 about a family in which 4 members carried the lamin A/C (LMNA) mutation n.644R>C and 3 members presented with left ventricular hypertrabeculation/noncompaction (LVHT). We have the following comments and concerns.
The authors describe the LMNA mutation as causative of LVHT. Although LVHT is frequently associated with mutations in various genes that encode for structural proteins, transport proteins, or enzymes in myocardial or muscle cells, none of these mutations has ever been proved to “cause” LVHT. One argument against a causal relation between the many mutated genes and LVHT is that a large number of different genes are associated with LVHT.2 Another argument is that a mutation is often present in various family members, but only one member presents with LVHT. Furthermore, a mutation might be associated with different myocardial manifestations in the same family, such as LVHT, hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmias, or sudden cardiac death.
Lamin A/C mutations not only cause cardiac disease, but also Emery-Dreifuss muscular dystrophy, limb-girdle muscular dystrophy, Dunnigan-type familial partial lipodystrophy, mandibuloacral dysplasia, Hutchinson-Gilford progeria syndrome, restrictive dermopathy, and autosomal recessive Charcot-Marie-Tooth disease type 2.3 Did the authors' patient develop muscular manifestations? Was he seen by a neurologist to investigate whether muscle, peripheral nerve, or other noncardiac tissues were clinically or subclinically involved?
The patient was reported to have experienced primary syncope. Were neurologic causes of syncope considered? Were cerebral magnetic resonance imaging (MRI), electroencephalography, and carotid ultrasound carried out? Because LVHT might be associated with stroke or embolism, it is essential to exclude ischemic stroke on cerebral MRI. What were the results of long-term blood pressure monitoring? Because systolic function was normal, there is no sufficient explanation for syncope.
De novo development of LVHT (acquired LVHT) is not unusual. It has been reported in patients with neuromuscular disorders (NMDs) and recently in pregnant women and professional athletes.4
Lamin A/C mutations have been reported not only in association with the authors' patient,1 but also in other patients with LVHT.3,5,6
Overall, this interesting case could profit from further investigations for neurologic disease, cardioembolism, and neurologic causes of syncope. The detection of a mutated gene does not necessarily imply causality of LVHT.
