Resources
Glossary
At a glancePlain-language definitions of terms used on this site.
- AFO (ankle-foot orthosis)
- A brace used to correct foot drop [6].
- Allelic conditions
- Different conditions caused by changes in the same gene. CMT2C, scapuloperoneal SMA and congenital distal SMA are allelic, as are the TRPV4 bone conditions: all are caused by changes in TRPV4 [6].
- Ankyrin repeat domain (ARD)
- The part of the TRPV4 protein, inside the cell, where most neuropathy mutations sit [6].
- Antagonist (inhibitor)
- A compound that blocks a channel. TRPV4 antagonists rescued fly and mouse models of the disease [15].
- Arthrogryposis
- Joint contractures (stiff joints that cannot fully bend or straighten) present from birth, reported in 33% of people in the TRPV4 registry [3].
- Autosomal dominant
- An inheritance pattern in which each child of an affected parent has a 50% chance of inheriting the variant [6].
- Axonal neuropathy (CMT type 2)
- Nerve disease in which the axon, the nerve's wire, is damaged and signal strength is reduced [9].
- BiPAP and CPAP
- Two different breathing machines, often used at night. BiPAP (bilevel) gives a higher pressure to breathe in and a lower one to breathe out, so it helps weak breathing muscles move air; a home ventilator does the same job with more setting options [288]. CPAP gives one constant pressure that holds the airway open but does not help weak breathing muscles, so it is not the right machine when they are weak [288]. See CPAP and weak breathing muscles.
- Blood-spinal cord barrier
- The protective lining of blood vessels in the spinal cord. In mice with TRPV4 mutations, it was disrupted in specific spots [15].
- CaMKII
- A calcium-activated enzyme. In a fly study, it had the strongest influence on how toxic mutant TRPV4 was [26].
- CDSMA (congenital distal spinal muscular atrophy)
- A TRPV4 condition present from birth, with leg weakness and contractures [6].
- ClinVar
- A free public database from the US National Library of Medicine that collects labs' classifications of genetic variants, with a star rating for how well each one has been reviewed [217]. See TRPV4 variants.
- CMTES (CMT Examination Score)
- A clinical severity score built from symptoms and examination findings, with 0 meaning no impairment. The standard version runs from 0 to 28 [95]. The TRPV4 registry used a weighted (Rasch) version that runs from 0 to 32: participants' mean score was 11, in the moderate range, and individual scores ranged from 0 to 22 [3].
- De novo variant
- A new genetic change not inherited from a parent. About 10% of CMT cases result from new variants [9].
- Demyelinating neuropathy (CMT type 1)
- Nerve disease in which the problem lies in myelin, the nerve's insulation, and signals are slowed [9].
- EMG and nerve conduction study
- Electrical tests of muscle and nerve. In CMT2C they show smaller motor responses with normal speeds, and signs of long-standing nerve damage (chronic neurogenic changes) [6].
- Endothelial cells
- Cells lining blood vessels. In mice, mutant TRPV4 in these cells drove the disease [15].
- Expanded access
- An FDA pathway that lets a physician request an investigational (not yet approved) drug for use outside a trial [43].
- Fast Track, Orphan Drug and Rare Pediatric Disease designations
- FDA designations that ABS-0871 has received [4].
- Gain of function
- A mutation that makes a protein overactive. The current consensus is that this is how neuromuscular TRPV4 variants cause disease [6].
- HMSN 2C
- Hereditary motor and sensory neuropathy type 2C, an older name for CMT2C [11].
- Laryngoscopy
- A camera examination of the vocal folds, recommended yearly in TRPV4 disease [6].
- Mosaicism
- Carrying a variant in only some of the body's cells, reported for TRPV4 in 2025 [20].
- Natural history study
- A study that follows people over time to learn how a disease behaves. For example, the INC 6601 study uses yearly visits [52].
- Non-length-dependent weakness
- Weakness that does not simply start in the feet, where the longest nerves end, and work upward. It can affect, for example, the shoulders or hips [6].
- Pathogenic variant
- A genetic change classified as disease-causing. Mine is TRPV4 p.Arg186Gln. See TRPV4 variants.
- Proband
- The person through whom a family first comes to the attention of doctors or researchers, usually the first family member to be diagnosed. Research papers describe the rest of the family in relation to the proband.
- Reclassification
- A change to a variant's classification after new evidence, such as family testing, lab studies or population data. In large studies by genetic testing labs, about 7 to 8% of VUS were reclassified within a few years, most of them to benign [210].
- Reduced penetrance
- Not everyone with the variant develops noticeable symptoms. Signs can be so mild that the person and their doctors do not recognize them, or appear only later in life [6].
- RhoA
- A regulatory protein that binds TRPV4 and restrains channel opening. Neuropathy mutations disrupt this binding [24].
- SARM1
- An enzyme that drives the axon’s built-in self-destruct program [31].
- Segregation
- Whether a variant travels with a condition in a family: carried by affected relatives and, ideally, not by unaffected ones. It is one kind of evidence used to classify variants [229].
- SPSMA (scapuloperoneal spinal muscular atrophy)
- A TRPV4 condition with weakness of the shoulder girdle and lower leg muscles [6].
- Stridor
- Noisy breathing caused by a narrowed airway, reported by 40% of registry participants [3].
- TRPV4
- A channel in the cell membrane that lets calcium in, and the gene that makes it. Changes in this gene cause CMT2C [10].
- Variant of uncertain significance (VUS)
- A genetic change without enough evidence to call it disease-causing or harmless. It neither confirms nor rules out a genetic cause, and it can be reclassified as evidence grows [205]. See TRPV4 variants.
- Vocal fold paresis
- Weakness of the vocal folds, diagnosed in 55% of people in the registry [3].