History

Fact Explanation
Difficulty in relaxing hand grasp Slow relaxation of muscles after contraction. [1,2]
Visual impairment Development of cataract due to same genetic defect as that causing muscle atrophy and myotonia. [1,2,3]
Difficulty in swallowing Weakness of muscles in pharynx. [1,2]
Loss of weight Due to muscle wasting. [2,4]
Impotence Due to hypogonadism with low testosterone levels. [5]
Baldness Same genetic defect on chromosome 19 causes baldness. [1,2]
Weakness in limbs Due to muscle wasting. [2]
Sudden falling like a log while walking Myotonia causing sudden inability to maintain balance. [1,2]
References
  1. VANIER TM. Dystrophia Myotonica in Childhood Br Med J [online] 1960 Oct 29, 2(5208):1284-1288 [viewed 06 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2097012
  2. ADIE W. J., GREENFIELD J. G.. DYSTROPHIA MYOTONICA (MYOTONIA ATROPHICA). Brain [online] 1923 December, 46(1):73-127 [viewed 06 August 2014] Available from: doi:10.1093/brain/46.1.73
  3. KLESERT TODD R., CHO DIANE H., CLARK JOHN I., MAYLIE JAMES, ADELMAN JOHN, SNIDER LAUREN, YUEN ERIC C., SORIANO PHILIPPE, TAPSCOTT STEPHEN J.. Mice deficient in Six5 develop cataracts: implications for myotonic dystrophy. Nat Genet [online] 2000 May, 25(1):105-109 [viewed 08 August 2014] Available from: doi:10.1038/75490
  4. RANUM LAURA P. W., RASMUSSEN PAUL F., BENZOW KELLIE A., KOOB MICHAEL D., DAY JOHN W.. . Nat. Genet. [online] 1998 June, 19(2):196-198 [viewed 08 August 2014] Available from: doi:10.1038/570
  5. MASTROGIACOMO I., BONANNI G., MENEGAZZO E., SANTAROSSA C., PAGANI E., GENNARELLI M., ANGELINI C.. Clinical and hormonal aspects of male hypogonadism in myotonic dystrophy. Ital J Neuro Sci [online] 1996 January, 17(1):59-65 [viewed 08 August 2014] Available from: doi:10.1007/BF01995710

Examination

Fact Explanation
Tapping the thenar eminence of hand causes a dimple which persists for a while Failure of immediate muscle relaxation after contraction has ceased. [1,2]
Ptosis Weakness of levator palpebrae superioris muscle. [1,2]
Atrophy of testicles Primary gonadal failure with high serum FSH and LH hormone levels and low testosterone levels. [4]
Atrophy of face and neck muscles Muscle atrophy due to triplet expansion in chromosome 19. [3]
Tapping the lateral border of tongue causes a deep dimple at the site of impact which persists for a while Due to persistent muscle contraction without immediate relaxation . [1,2]
Tachycardia or bradycardia or irregular pulse Due to fibrosis and fatty infiltration of conducting system and AV node. [1,2]
References
  1. ADIE W. J., GREENFIELD J. G.. DYSTROPHIA MYOTONICA (MYOTONIA ATROPHICA). Brain [online] 1923 December, 46(1):73-127 [viewed 06 August 2014] Available from: doi:10.1093/brain/46.1.73
  2. PHILLIPS M. Cardiac disease in myotonic dystrophy. [online] 1997 January, 33(1):13-22 [viewed 08 August 2014] Available from: doi:10.1016/S0008-6363(96)00163-0
  3. RANUM LAURA P.W., DAY JOHN W.. Myotonic Dystrophy: RNA Pathogenesis Comes into Focus. The American Journal of Human Genetics [online] 2004 May, 74(5):793-804 [viewed 08 August 2014] Available from: doi:10.1086/383590
  4. HARPER PETER, PENNY ROBERT, FOLEY THOMAS P., MIGEON CLAUDE J., BLIZZARD ROBERT M.. Gonadal Function in Males with Myotonic Dystrophy . The Journal of Clinical Endocrinology & Metabolism [online] 1972 December, 35(6):852-856 [viewed 08 August 2014] Available from: doi:10.1210/jcem-35-6-852

Differential Diagnoses

Fact Explanation
Myotonia congenita Presents with generalized myotonia and stiffness. Muscles are prominent and there are no extra muscular abnormalities. [1]
Recessive generalized myotonia Presents at the age of 4 to 12 years with symptoms of myotonia mainly in legs. Muscle hypertrophy is common. [1]
Paramyotonia congenita Characterized by muscle stiffness that is triggered or worsened by cold weather. Repeated muscle contractions lead to flaccid paralysis. [1]
Hyperkalemic periodic paralysis with myotonia Presents with stiffness and paralysis. Can be triggered by rest following exercise, cold and hunger. [1]
References
  1. STREIB ERICH W.. AAEE minimonograph #27: Differential diagnosis of myotonic syndromes. Muscle Nerve [online] 1987 September, 10(7):603-615 [viewed 08 August 2014] Available from: doi:10.1002/mus.880100704

Investigations - for Diagnosis

Fact Explanation
Electromyography This shows a combination of myotonic discharges and myopathic appearing motor units. Characteristic bursts of repetitive potentials which vary both in potential and frequency are called "dive bomber" potentials. [1]
Serum creatinine level May be mildly elevated. [1]
Muscle biopsy This is histologically grossly abnormal in clinically affected patients. Features include fibrosis, variability in fiber size, sarcoplasmic masses etc. [1]
Genetic testing (Polymerase chain reaction and southern blotting) This is the mainstay of diagnosis. It shows the CTG trinucleotide repeat expansion in gene which codes for a myosine kinase expressed in skeletal muscle. [1]
References
  1. TURNER C., HILTON-JONES D.. The myotonic dystrophies: diagnosis and management. Journal of Neurology, Neurosurgery & Psychiatry [online] December, 81(4):358-367 [viewed 08 August 2014] Available from: doi:10.1136/jnnp.2008.158261

Investigations - Followup

Fact Explanation
ECG Should be done yearly to detect cardiac arrhythmia. [1]
Sleep study For any symptoms of excessive daytime sleepiness and obstructive sleep apnoea. [1]
Fasting blood sugar There is no significant increase in incidence of diabetes mellitus among patients with Dystrophia Myotonica compared to the general population. However there is evidence of insulin resistance due to abnormal splicing of the insulin receptor mRNA to a more insulin insensitive isoform. Therefore any clinical suspicion of diabetes mellitus should prompt a fasting blood sugar test. [2]
References
  1. TURNER C., HILTON-JONES D.. The myotonic dystrophies: diagnosis and management. Journal of Neurology, Neurosurgery & Psychiatry [online] December, 81(4):358-367 [viewed 08 August 2014] Available from: doi:10.1136/jnnp.2008.158261
  2. TAKASE SADAO, OKITA NAOSHI, SAKUMA HIROAKI, MOCHIZUKI HIROSHI, OHARA YOSHIRO, MIZUNO YASUJI, SATO TOKUTARO, HANEW KUNIHIKO. Endocrinological abnormalities in myotonic dystrophy: Consecutive studies of eight tolerance tests in 26 patients.. Tohoku J. Exp. Med. [online] 1987 December, 153(4):355-374 [viewed 09 August 2014] Available from: doi:10.1620/tjem.153.355

Investigations - Screening/Staging

Fact Explanation
Prenatal molecular diagnosis This can be done using retrieved transcervical trophoblastic cells or maternal plasma. [1]
References
  1. MASSARI A., NOVELLI G., COLOSIMO A., SANGIUOLO F., PALKA G., CALABRESE G., CAMURRI L., GHIRARDINI G., MILANI G., GIORLANDINO C., GAZZANELLI G., MALATESTA M., ROMANINI C., DALLAPICCOLA B.. Non-invasive early prenatal molecular diagnosis using retrieved transcervical trophoblast cells. Hum Genet [online] 1996 February, 97(2):150-155 [viewed 08 August 2014] Available from: doi:10.1007/BF02265257

Management - General Measures

Fact Explanation
Dehydroepiandrosterone (DHEA) Initial pilot studies suggested improvement of muscle power. But a recent multicentre, randomised, double-blind. placebo controlled study did not substantiate this. [1]
Exercise training This can maximize muscle and cardio respiratory function and prevent disuse atrophy of muscles. [2,3]
Sodium channel blockers Myotonia is the main cause of disability in patients with dystrophia myotonica.Myotonia could be caused by inactivation defect of Sodium channels causing long-lasting depolarisation of the muscle fiber. Thus blocking these channels can relieve myotonia. [3]
Benzodiazepines: Diazepam Probably due to membrane stabilizing effect. [4]
Calcium antagonists: Nifedipine High concentrations of Calcium have been found in red blood cells and skeletal muscle in myotonic dystrophy. Thus by blocking calcium channels myotonia gets relieved. [9]
CNS stimulant drugs Modafinil 200-400 mg/day - The mechanism of action of modafinil is still not completely understood, but it is associated with an activation of the tuberomamillary nucleus and orexin-containing neurons. Methylphenidate and Dexamphetamine: these drugs are useful in the sleep disordered. breathing. [5]
Dietary manipulation Thickening food, adding supplements and adopting safer swallowing techniques help to overcome dysphagia. [6]
Tricyclic anti depressive drugs: Imipramine, Clomipramine It has been hypothesized that myotonic dystrophy is caused by a generalized disorder of membrane aminergic and petidergic receptors. Thus Inhibition of re uptake of neurotransmitters can benefit myotonia. [7,8]
References
  1. SUGINO M., OHSAWA N., ITO T., ISHIDA S., YAMASAKI H., KIMURA F., SHINODA K.. A pilot study of dehydroepiandrosterone sulfate in myotonic dystrophy. Neurology [online] 1998 August, 51(2):586-589 [viewed 08 August 2014] Available from: doi:10.1212/WNL.51.2.586
  2. PENISSON-BESNIER I., DEVILLERS M., PORCHER R., ORLIKOWSKI D., DOPPLER V., DESNUELLE C., FERRER X., BES M. -C.A., BOUHOUR F., TRANCHANT C., LAGRANGE E., VERSHUEREN A., UZENOT D., CINTAS P., SOLE G., HOGREL J. -Y., LAFORET P., VIAL C., VILA A. L., SACCONI S., POUGET J., EYMARD B., CHEVRET S., ANNANE D.. Dehydroepiandrosterone for myotonic dystrophy type 1. Neurology [online] 2008 August, 71(6):407-412 [viewed 08 August 2014] Available from: doi:10.1212/01.wnl.0000324257.35759.40
  3. LINDEMAN ELINE, LEFFERS PIETER, SPAANS FRANK, DRUKKER JAN, REULEN JOS, KERCKHOFFS MARIA, KöKE ALBERE. Strength training in patients with myotonic dystrophy and hereditary motor and sensory neuropathy: A randomized clinical trial. Archives of Physical Medicine and Rehabilitation [online] 1995 July, 76(7):612-620 [viewed 08 August 2014] Available from: doi:10.1016/S0003-9993(95)80629-6
  4. TURNER C., HILTON-JONES D.. The myotonic dystrophies: diagnosis and management. Journal of Neurology, Neurosurgery & Psychiatry [online] December, 81(4):358-367 [viewed 08 August 2014] Available from: doi:10.1136/jnnp.2008.158261
  5. MACDONALD J. R., HILL J. D., TARNOPOLSKY M. A.. Modafinil reduces excessive somnolence and enhances mood in patients with myotonic dystrophy. Neurology [online] 2002 December, 59(12):1876-1880 [viewed 08 August 2014] Available from: doi:10.1212/01.WNL.0000037481.08283.51
  6. TALBOT K, STRADLING J, CROSBY J, HILTON-JONES D. Reduction in excess daytime sleepiness by modafinil in patients with myotonic dystrophy. Neuromuscular Disorders [online] 2003 June, 13(5):357-364 [viewed 08 August 2014] Available from: doi:10.1016/S0960-8966(03)00030-0
  7. MOTLAGH BAHAREH, MACDONALD JAY R., TARNOPOLSKY MARK A.. Nutritional inadequacy in adults with muscular dystrophy. Muscle Nerve [online] December, 31(6):713-718 [viewed 08 August 2014] Available from: doi:10.1002/mus.20317
  8. TAKASE SADAO, OKITA NAOSHI, SAKUMA HIROAKI, MOCHIZUKI HIROSHI, OHARA YOSHIRO, MIZUNO YASUJI, SATO TOKUTARO, HANEW KUNIHIKO. Endocrinological abnormalities in myotonic dystrophy: Consecutive studies of eight tolerance tests in 26 patients.. Tohoku J. Exp. Med. [online] 1987 December, 153(4):355-374 [viewed 09 August 2014] Available from: doi:10.1620/tjem.153.355
  9. GRANT R, SUTTON D L, BEHAN P O, BALLANTYNE J P. Nifedipine in the treatment of myotonia in myotonic dystrophy.. Journal of Neurology, Neurosurgery & Psychiatry [online] 1987 February, 50(2):199-206 [viewed 09 August 2014] Available from: doi:10.1136/jnnp.50.2.199

Management - Specific Treatments

Fact Explanation
Gene therapy This is the only mode of definitive treatment. However this option is still at in vitro experimental level. [1,2]
References
  1. LANGLOIS M. Hammerhead ribozyme-mediated destruction of nuclear foci in myotonic dystrophy myoblasts. Molecular Therapy [online] 2003 May, 7(5):670-680 [viewed 08 August 2014] Available from: doi:10.1016/S1525-0016(03)00068-6
  2. FURLING D, DOUCET G, LANGLOIS M-A, TIMCHENKO L, BELANGER E, COSSETTE L, PUYMIRAT J. Viral vector producing antisense RNA restores myotonic dystrophy myoblast functions. Gene Ther [online] 2003 May, 10(9):795-802 [viewed 08 August 2014] Available from: doi:10.1038/sj.gt.3301955