Abstract Details

Title Co-occurrence of Two Distinct Genetic Disorders in One Family, with Both Disorders Occurring in One Member

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P10 - Poster Session 10 (5:00 PM-6:00 PM)

Poster/Presentation
Number 11-018

Objective To report a family with coexistence of 2 rare, unrelated neurologic disorders.

Background Advances in genetic diagnosis have provided insights into phenotypic and genotypic heterogeneity of many disorders with proper identification of atypical clinical pictures. We present a family with two distinct genetically proven neurologic disorders, with both disorders occurring in one member.

Design/Methods Case-report of family members seen in neuromuscular clinic who underwent genetic testing.

Results Three family members were evaluated for progressive neurologic symptoms. A 59-year-old woman presented with gait difficulty, spasticity, and brisk reflexes. After ruling out acquired causes of myelopathy, genetic testing confirmed a spastin mutation consistent with autosomal dominant hereditary spastic paraplegia (SPG4). Her 63-year-old sister, followed in the same clinic, was previously diagnosed with genetically confirmed myotonic dystrophy type 1 (DM1) at age 49 after developing progressive weakness and impaired fine motor control. On neurologic exam, she also had brisk reflexes and ankle clonus. A workup for acquired etiologies of the brisk reflexes was unrevealing. After SPG4 was diagnosed in her sister, she underwent focused genetic testing which confirmed a concurrent spastin mutation. Their 58-year-old brother is followed for gait difficulty and bulbar weakness with a genetically confirmed diagnosis of DM1. He does not exhibit signs of HSP such as brisk reflexes or spasticity, so further testing was not performed. Clinical details and investigations will be presented.

Conclusions The presence of atypical findings in patients and family members with known genetic disorders should prompt evaluation for concurrent genetic disorders after excluding acquired etiologies. Knowledge of phenotypes of rare disorders and a careful clinical examination therefore remain essential, especially as novel treatments for genetic disorders are developed.

Authors/Disclosures
Karthik Jagannath, MD (BIDMC) PRESENTER	Dr. Jagannath has nothing to disclose.
Pushpa Narayanaswami, MD, MBBS, FAAN (Beth Israel Deaconess Medical Center)	Dr. Narayanaswami has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for UCB. Dr. Narayanaswami has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CVS. Dr. Narayanaswami has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Narayanaswami has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. Dr. Narayanaswami has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx USA. Dr. Narayanaswami has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Narayanaswami has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. Dr. Narayanaswami has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for NMD pharma. Dr. Narayanaswami has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD-Serono (Merck usa). Dr. Narayanaswami has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Immuneabs. Dr. Narayanaswami has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Viridian. Dr. Narayanaswami has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cabaletta-Bio. Dr. Narayanaswami has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunovant. Dr. Narayanaswami has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen. Dr. Narayanaswami has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Dianthus. Dr. Narayanaswami has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cartesian. Dr. Narayanaswami has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vor Bio. Dr. Narayanaswami has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Muscle and Nerve, Wiley. Dr. Narayanaswami has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology. Dr. Narayanaswami has or had stock in Dr. Reddys laboratories.Dr. Narayanaswami has or had stock in Doximity. The institution of Dr. Narayanaswami has received research support from Alexion. The institution of Dr. Narayanaswami has received research support from NIH. The institution of Dr. Narayanaswami has received research support from Argenx. The institution of Dr. Narayanaswami has received research support from Cabaletta Bio. Dr. Narayanaswami has received publishing royalties from a publication relating to health care. Dr. Narayanaswami has a non-compensated relationship as a Member, Finance Committee with AANEM that is relevant to AAN interests or activities.

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