WBR0303

Author	[[PageAuthor::William J Gibson (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Genetics
Sub Category	SubCategory::Neurology, SubCategory::General Principles
Prompt	[[Prompt::A 26-year-old man presents to his primary care physician with complaints of muscle weakness. The patient used to partake in vigorous exercise, but over the past year has noted a gradual decline in his strength. He explains that he can no longer hold his body weight on the pull-up bar at the gym. Upon further questioning, the patient also reports he is sometimes unable to release his grip from a doorknob. On physical examination, the physician notes the patient has dysarthric speech and is unable to reverse the contraction of his thumb following percussion of the thenar eminence. What is the mode of inheritance of this patient's condition?]]
Answer A	AnswerA::Autosomal recessive
Answer A Explanation	AnswerAExp::Myotonic dystrophy is not an autosomal recessive disorder. An example of an autosomal recessive disease is phenylketonuria.
Answer B	AnswerB::Autosomal dominant
Answer B Explanation	AnswerBExp::Myotonic dystrophy is an autosomal dominant disorder.
Answer C	AnswerC::X-linked dominant
Answer C Explanation	AnswerCExp::Myotonic dystrophy is not an X-linked dominant disorder. An example of an X-linked dominant disorder is Rett syndrome.
Answer D	AnswerD::X-linked recessive
Answer D Explanation	AnswerDExp::Myotonic dystrophy is not an X-linked recessive disorder. An example of an X-linked recessive disorder is Duchenne muscular dystrophy (DMD)
Answer E	AnswerE::Mitochondrial inheritance
Answer E Explanation	AnswerEExp::Myotonic dystrophy is not a mitochondrial disorder. An example of a mitochondrial disorder is Leber’s hereditary optic neuropathy.
Right Answer	RightAnswer::B
Explanation	[[Explanation::Myotonic dystrophy subtype 1 (DM1 or MMD1 or Steinert's disease) is a autosomal dominant genetic disorder characterized by progressive distal muscle weakness of the upper and lower extremities. Patients often complain of foot drop or inability to perform physical activities that require intricate use of the hands (use tools or doorknobs). In addition, patients with myotonic dystrophy have frontal balding and unique facial features (temporal wasting and hatchet-appearance) caused by the wasting of the facial muscles and also resulting in ptosis and dysarthria. Patients may exhibit a "warm-up phenomenon", characterized by the improvement in strength of the handgrip myotonia upon repeated contractions (e.g. inability to release hand from doorknob following contraction). On physical examination, percussion myotonia may also be evaluated by percussion of the thenar eminence using a tendon hammer. Patients with myotonic dystophy are at-risk of several complications, including subcapsular cataracts, which eventually develop in almost all patients, cardiac conduction abnormalities (potentially fatal tachyarrhythmias), aspiration pneumonia and diaphragmatic weakness, endocrinopathies, intellectual deficits, cholecystitis and decreased esophageal peristalsis (increased tonicity of gallbladder sphincter and esophageal muscles, respectively), slow gastric emptying, constipation (may be due to pseudo-obstruction), or diarrhea and fecal incontinence. Myotonic dystophy has 2 subtypes: DM1 or MMD1 (Steinert's disease): Autosomal dominant disorder characterized by the presence of unstable CTG trinucleotide repeats (5' CTG 3') in the 3' untranslated region of the DMPK (myotonic dystrophy protein kinase) gene in chromosome 19q that normally encodes myosin kinase. The number of CTG repeats is directly associated with the clinical manifestations of the disease; normal individuals have less than 37 CTG repeats, asymptomatic patients with a pre-mutation have 37-50 CTG repeats, and patients with clinical myotonic distrophy have > 50 CTG repeats. The disease is characterized by anticipation, whereby children of patients with a pre-mutation (37-50 CTG repeats) may have longer repeats and develop manifestations of the disease. DM2 or MMD2 (proximal myotonic myopathy): Autosomal dominant disorder caused by a mutation of ZNF9 (zinc finger protein) gene in chromosome 3q that result in the expansion of CCTG (not CTG) repeats. Unlike DM1, the number of CCTG repeats does not correlate with the clinical manifestations of DM2. Symptoms begin at adulthood, including myotonia and proximal weakness, stiffness, and fatigue. Although it shares similar complications to DM1, DM2 is considered a milder disease. DM2 is not usually tested on USMLE. Educational Objective: Myotonic dystrophy subtype 1 (DM1 or MMD1) is a autosomal dominant genetic disorder characterized by progressive distal muscle weakness of the upper and lower extremities. Patients often complain of foot drop or inability to perform physical activities that require intricate use of the hands (use tools or doorknobs). References: Turner C, Hilton-Jones D. The myotonic dystrophies: diagnosis and management. J Neurol Neurosurg Psychiatry. 2010;81:358-67. First Aid 2014 page 89]]
Approved	Approved::Yes
Keyword	WBRKeyword::Myotonic dystrophy, WBRKeyword::Genetics, WBRKeyword::Trinucleotide repeat disorders, WBRKeyword::CTG repeats, WBRKeyword::Steinert's disease, WBRKeyword::DM1, WBRKeyword::MMD1, WBRKeyword::Autosomal dominant, WBRKeyword::Temporal wasting, WBRKeyword::Hatchet appearance, WBRKeyword::Myotonic handgrip, WBRKeyword::Myotonic percussion
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