Expert Reviewed By: Dr. Brandon Colby MD
Spastic paraplegia is a group of rare genetic disorders characterized by progressive weakness and stiffness in the leg muscles. Autosomal dominant spastic paraplegia (ADSP) is a form of the disease inherited in an autosomal dominant manner, meaning that an affected individual has a 50% chance of passing the condition to their offspring. This article aims to shed light on understanding, diagnosing, and using genetic testing for autosomal dominant spastic paraplegia, with a focus on recent scientific advancements.
Understanding Autosomal Dominant Spastic Paraplegia
Spastic paraplegia, also known as hereditary spastic paraplegia (HSP), is a group of inherited neurological disorders that primarily affect the upper motor neurons in the brain and spinal cord. These neurons are responsible for transmitting signals from the brain to the muscles, enabling voluntary movement. Damage to the upper motor neurons leads to muscle weakness, stiffness, and reduced mobility in the lower limbs.
Autosomal dominant spastic paraplegia is caused by mutations in specific genes, which are passed down through families. Researchers have identified several genes associated with ADSP, including the SPAST, ERLIN2, and ALDH18A1 genes1,2,3. These genes play crucial roles in various cellular processes, such as maintaining the structure and function of nerve cells, regulating lipid metabolism, and synthesizing proteins.
Diagnosing Autosomal Dominant Spastic Paraplegia
The diagnosis of autosomal dominant spastic paraplegia typically begins with a thorough clinical evaluation, including a detailed patient history and neurological examination. The physician may also order imaging studies, such as magnetic resonance imaging (MRI) of the brain and spinal cord, to rule out other potential causes of the symptoms.
However, the definitive diagnosis of ADSP relies on genetic testing. This involves analyzing the DNA of the affected individual to identify mutations in the associated genes. Genetic testing not only confirms the diagnosis but also provides valuable information for genetic counseling and family planning purposes.
Genetic Testing for ERLIN2 Mutations
A recent study identified a novel heterozygous variant in the ERLIN2 gene as the cause of autosomal dominant pure HSP in two large, unrelated non-consanguineous families1. This discovery highlights the importance of genetic testing in diagnosing ADSP and furthering our understanding of the underlying genetic causes.
Genetic Testing for ALDH18A1 Mutations
Another study expanded the genetic and clinical spectrum of a specific subtype of autosomal recessive spastic paraplegia (SPG9B) caused by ALDH18A1 mutations2. The researchers demonstrated the informative value of splicing mutation prediction, a technique used to identify mutations that disrupt the normal processing of RNA molecules, which are essential for protein synthesis.
Genetic Testing for SPAST Mutations
Research conducted in the Republic of Bashkortostan documented a major mutation in the SPAST gene in patients with autosomal dominant spastic paraplegia3. This finding further emphasizes the significance of genetic testing in diagnosing ADSP and understanding the genetic basis of the disease.
Using Genetic Testing to Manage Autosomal Dominant Spastic Paraplegia
Genetic testing plays a crucial role in the management of autosomal dominant spastic paraplegia. It not only confirms the diagnosis but also provides essential information for genetic counseling and family planning. By understanding the specific genetic mutations responsible for ADSP, researchers can develop targeted therapies and interventions to improve the quality of life of affected individuals.
Moreover, genetic testing can help identify carriers of the mutated genes, allowing for informed reproductive decisions and early intervention strategies for at-risk family members. As our understanding of the genetic basis of autosomal dominant spastic paraplegia continues to grow, so too does the potential for improved diagnostic and treatment options for those living with this rare neurological disorder.
1 A novel heterozygous variant in ERLIN2 causes autosomal dominant pure hereditary spastic paraplegia
About The Expert Reviewer
Dr. Brandon Colby MD is a US physician specializing in the personalized prevention of disease through the use of genomic technologies. He’s an expert in genetic testing, genetic analysis, and precision medicine. Dr. Colby is also the Founder of and the author of Outsmart Your Genes.
Dr. Colby holds an MD from the Mount Sinai School of Medicine, an MBA from Stanford University’s Graduate School of Business, and a degree in Genetics with Honors from the University of Michigan. He is an Affiliate Specialist of the American College of Medical Genetics and Genomics (ACMG), an Associate of the American College of Preventive Medicine (ACPM), and a member of the National Society of Genetic Counselors (NSGC)