Case Study: Neurology
Mr. Jones is a 60-year-male with a history of proximal muscle weakness, elevated CK, and loss of muscle mass. He reports issues with muscle weakness and fatigue dating back to high school when he had difficulty with sports. His workup has included muscle biopsies and EMG, which were indicative of myopathy. He reports that he has attempted to build muscle mass through exercise but is unable to do so and suffers fatigue after workouts. Mr. Jones is referred to a genomics clinic for further evaluation.
Case Study: Pediatric Neurology
Marcus is a 3-year-old male with a history of severe speech delay, hypotonia, ocular strabismus and a working diagnosis of cerebral palsy. He has some minor facial dysmorphology that is not suggestive of a specific condition. To date, Marcus has had a normal brain MRI examination as well as baseline genetic testing (karyotype, microarray, and fragile X syndrome) none of which provided an explanation for his symptoms. Marcus is referred to a genomics clinic for further evaluation.
Case Study: Pediatrics
A patient presents with vision loss, obesity, renal failure, and cognitive deficits. Genomic sequencing identifies a variant in the BBS10 gene. The BBS10 gene is associated with Bardet-Biedl syndrome and is consistent with all of the clinical features in the patient. In addition, the specific variant has been repeatedly described in the literature in patients diagnosed with Bardet-Biedl syndrome. Based on this evidence, the variant would be classified as pathogenic. In contrast, if sequencing identified a different variant in BBS10 that had not been previously observed in either healthy or symptomatic populations, the variant would probably be classified as “likely pathogenic.” With time and as more individuals are sequenced, many “likely pathogenic” variants are reclassified to “pathogenic.”
Case Study: Ophthalmology
James is a 47-year-old man with retinitis pigmentosa (RP), a group of rare, genetic disorders that cause the retina to degenerate. RP causes light sensitivity and vision problems such as difficulty seeing at night and loss of peripheral vision. Although he already has a clinical diagnosis, James contacts a genomics clinic to learn more about his particular form of RP.
Because James already has a clinical diagnosis, the geneticist orders a gene panel to look at a specific set of genes that are associated with retinitis pigmentosa. The panel reveals a likely pathogenic variant in both copies of James’s USH2A gene, which provides instructions for making a protein that is essential for normal vision.
Next Steps to Consider
With this information, James has more insight about the cause of his symptoms and his prognosis and can look into possible clinical trials and new treatment options. In addition, he now knows that while his children will be carriers for the condition, their chance to have RP is very low.
Case Study: Immunology
April is a 45-year-old woman with a lifelong history of rash, fever and aching joints, but only when exposed to the cold. After more than 40 years of doctors appointments, incorrect diagnoses, and an unnecessary surgery, April contacts a genomics clinic to get a molecular diagnosis and, hopefully, a treatment.
Because her symptoms do not suggest a specific genetic disorder, genome sequencing is recommended to explore her entire genetic code. This test reveals a disease-causing variant in the NLRP3 gene, which is associated with familial cold autoinflammatory syndrome or FCAS. FCAS is a very rare condition that causes fever, skin rash and joint pain when exposed to cold temperatures.
Next Steps to Consider
With a correct diagnosis in hand, April can work with an immunologist and look at possible medications for treating her FCAS. Now that she has documented evidence of her condition, insurance is more likely to cover the cost of medication. This information can also determine the likelihood that her children and other relatives share this NLRP3 gene change and allow them to be tested to determine whether they are at risk of developing this same condition in the future.