Clinical Data of DM1 Variant Patients

Clinical data of DM1 variant patients

Patient 1 (Pt1), a 63-year-old woman had noticed over the past fifteen years handgrip myotonia and progressive weakness and wasting in her distal lower limbs muscles. She did not complain of any suggestive cardiac symptom, but her father died at the age of 63 with a clinical diagnosis of

Morgagni-Adams-Stokes syndrome. Neurological examination showed a mild facial weakness, spontaneous and percussion hand-grip myotonia, severe wasting and weakness of distal limbs muscles with a bilateral steppage, more pronounced in the right leg, and a mild weakness of proximal lower limb muscles.

EMG studies showed electrical myotonia and myopathic signs. Nerve conduction studies and neuropsychological evaluation were normal. Ophthalmologic examination showed bilateral cataracts of the sub capsular type.

Respiratory function tests and tone audiometry were normal.

Endocrinologic assessment allowed to diagnose a follicular thyroid adenoma, successfully treated with surgery.

Non invasive ECG studies showed sinus bradycardia and a right bundle branch block and transient ischemic signs. Myocardial scintigraphy did not document perfusion defects. Echocardiography was normal too (FE > 60%).

Muscle MRI showed a diffuse fatty-fibrous replacement, more severe in the distal lower limb muscles (not shown).

During a two-years follow-up the patient has been showing substantially stable clinical and diagnostic parameters.

Patient 2 (Pt2), a 52-year-old woman, had noticed, about five years before, handgrip myotonia and proximal muscle weakness. Her father had frontal baldness and died at age 50 for sudden cardiac death. Neurological examination at age 50 revealed a narrow face with a mild blepharoptosis and a moderate facial weakness, jaw and handgrip myotonia, weakness of the neck flexors and the anterior fasces of deltoid muscles (F=3.5 MRC scale). She also had a mild difficulty to stand on her heels.

EMG studies showed electrical myotonia and myopathic signs. Nerve studies were normal

Ophthalmologic examination showed bilateral cataracts of the sub capsular type.

Tone audiometry was normal.

Muscle MRI documented a mild to moderate fatty-fibrous tissue replacement, associated with T2- hyperintensity of the leg and posterior thigh muscles, while a severe fatty-fibrous tissue replacement involved the paraspinal muscles (not shown). Respiratory function and neuropsychological tests were both normal.

Echocardiography was normal. Holter ECG documented a 1st degree atrio-ventricular block (AVB) and frequent nocturnal episodes of bradycardia that recommended an EPS. Results of EPS required a prophylactic implant of a pace-maker (PM). During the following year the patient experienced episodes of palpitations: the PM recorded two runs of asymptomatic non sustained ventricular tachycardia (NSVT), therefore she underwent an upgrading of the PM device to an intra-cardiac defibrillator (ICD).

Patient 3 (Pt3), a 70-year-old woman, from age 30 progressively developed a bilateral blepharoptosis. In the last five years she also noticed weakness and wasting in her limb muscles.

She had performed eye surgery for blepharoplastic procedures and bilateral cataracts.

She also was diagnosed with hypothyroidism and type II diabetes, and she referred to have suffered in the past of fertility problems and myocardial infarction. Her 60 years-old brother had diabetes and cataracts too.

Neurological evaluation showed bilateral ptosis, moderate facial weakness, mild handgrip myotonia, weakness and wasting of forearm and leg muscles with a bilateral steppage , and severe weakness of neck and axial muscles.

EMG studies showed electrical myotonia and myopathic signs. Nerve studies were normal.

Echocardiography documented a mild left ventricular hypertrophy and a 60% ejection fraction.

Basal and Holter ECG studies documented a 1st degree AV block plus a right bundle branch block and ischemic changes related to the past MI.

Neuropsychological evaluation documented a mild impairment of executive functions.

Respiratory function tests showed normal parameters. Because of increased daytime sleepiness the patient underwent a nocturnal pulse-oximetry documenting a percentage of O2 saturation between

90 and 98 %, and an arterial blood gas test showing a mild hypoxemia (79.50 mmHg) with normal

CO2, attributed to altered lung alveolar exchanges.

Patient 4 (Pt4), a 32-year-old man manifested from age 28 progressive weakness of facial and hand muscles. His mother, his sister and his maternal aunt were all referred to be similarly affected and his grandmother had premature cataract and died of cardiac causes in her seventies. He had multiple thyroid nodules associated with normal hormonal levels.

Neurological examination showed frontal baldness, a severe weakness of facial and neck flexors muscles, bilateral winging scapula and mild upper limb distal muscle weakness, while he had no clinical myotonia nor lower limb weakness. His ophthalmologic, audiometric and pneumological examinations were normal. He received a prophylactic PM implant according to the results of EPS

(performed because of the evidence of a 1st degree AV block, P-R interval = 240 msec) that documented a H-V interval > 70 msec. During the cardiologic follow-up, he manifested episodic sustained ventricular tachycardia, so three years later the PM was upgraded to ICD. For the persistence of frequent symptomatic ventricular premature beats, the patients was also treated with beta-blockers.

Patient 5 (Pt5), a 78-years-old male, manifested since his twenties handgrip myotonia, whereas symptomatic muscle weakness involving facial, bulbar and limb muscles became evident only around the age of 65 years. At age 52 he underwent surgery for cataracts. He was also affected by peripheral arteriopathy related to tabagism. Two of his sisters, also likely to be affected, died of cardiac causes at the age of 67 and 63 respectively.

Neurological examination showed a severe facial muscle weakness, nasal speech, dysphagia, handgrip myotonia, and a severe axial weakness and a moderate, diffuse limb muscle weakness. At the time of diagnosis, when he was 68 year old, ECG-Holter monitoring revealed a first degree A-V block, and pulmonary function tests showed findings consistent with mild restrictive lung disease.

Neuropsychological tests were normal. Tone audiometry revealed in this patient a mild bilateral sensory-neural hearing loss.

After seven years of follow-up, he developed a significant worsening of respiratory function with nocturnal and diurnal desaturations, requiring non-invasive ventilation (NIV) during sleep; also, he recently received a loop recorder because of syncope episodes not associated with significant abnormalities at an extensive diagnostic cardiologic assessment also including an EPS (H-V interval

= 70 msec).