Both 5q-linked spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD) are fatal monogenic neuromuscular disorders caused by loss-of-function mutations. SMA is an autosomal recessive disorder affecting motor neurons that is typically caused by homozygous whole-gene deletions of SMN1. DMD is an X-linked recessive muscle disease most often due to exon deletions, but also duplications and smaller sized variants within the DMD gene. Gene replacement therapy offers the opportunity to correct the underlying genetic defect by the introduction of a functional gene. We review the transformative work from clinical trials to United States Food and Drug Administration approval of onasemnogene abeparvovec-xioi in SMA and its application in clinical practice and the early results of microdystrophin delivery in DMD. We also review the introduction of antisense oligonucleotides to alter pre-mRNA splicing to promote exon inclusion (as in nusinersen in SMA) or exclusion (as in eteplirsen in DMD) into neuromuscular therapeutics. There are multiple promising novel genetically mediated therapies on the horizon, which in aggregate point towards a hopeful future for individuals with SMA and DMD.
Both 5q‐linked spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD) are fatal monogenic neuromuscular disorders caused by loss‐of‐function mutations. SMA is an autosomal recessive disorder affecting motor neurons that is typically caused by homozygous whole‐gene deletions of SMN1. DMD is an X‐linked recessive muscle disease most often due to exon deletions, but also duplications and smaller sized variants within the DMD gene. Gene replacement therapy offers the opportunity to correct the underlying genetic defect by the introduction of a functional gene. We review the transformative work from clinical trials to United States Food and Drug Administration approval of onasemnogene abeparvovec‐xioi in SMA and its application in clinical practice and the early results of microdystrophin delivery in DMD. We also review the introduction of antisense oligonucleotides to alter pre‐messenger RNA splicing to promote exon inclusion (as in nusinersen in SMA) or exclusion (as in eteplirsen in DMD) into neuromuscular therapeutics. There are multiple promising novel genetically mediated therapies on the horizon, which in aggregate point towards a hopeful future for individuals with SMA and DMD.
Objectives While national medical guidelines recommend genetic testing for all individuals with non-syndromic autism spectrum disorder (ASD), there is underutilization of genetic testing. This study aims to define the perspectives and approaches to initial genetic testing of ASD diagnosticians in order to improve utilization. Methods A prospective cross-sectional study was conducted using an anonymous online survey distributed to 59 staff neurologists, developmental-behavioral pediatricians, psychologists, post-graduate physician fellows, and nurse practitioners from a single academic medical center. Questions explored knowledge, attitudes, and practices of initial genetic testing for ASD among diagnosticians. Results Among the 30 respondents (51% response rate), a lack of comprehensive pre-test genetic counseling was identified and forgetfulness was the most prevalent reason for not recommending genetic testing (n = 7/23, 30%). Insurance prior authorization (PA) for genetic testing was a major barrier for clinicians. More than half of respondents (n = 13/25, 52%) reported being uncomfortable with the PA process. Conclusions Variability in knowledge and practices among ASD diagnosticians regarding genetic testing was identified. Therefore, potential interventions like clinician and administrative staff education, as well as genetic counselor integration into ASD clinics, may be useful to improve genetic testing utilization.
While inguinal hernia is common in the primary care office, the differential diagnosis is extensive and includes infectious, inflammatory and neoplastic processes. Varicocele is another frequent, generally benign condition which occasionally reflects serious disease entities. Left-sided or bilateral varicoceles account for the overwhelming majority of varicoceles because the left gonadal vein drains into the left renal vein in contrast to the right gonadal vein, which drains directly into the inferior vena cava, thus making left-sided or bilateral venous congestion more likely. Presence of an uncommon unilateral right-sided varicocele thus warrants further radiological workup, in particular CT abdomen and pelvis, to evaluate for retroperitoneal pathology. We describe a case in which appropriate use of a variety of imaging modalities including testicular ultrasound and CT led to an important diagnosis of a large, well-differentiated liposarcoma in the right retroperitoneum of a patient with a right-sided groin mass.
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