Usher syndrome is also known as:

  • Hallgren syndrome
  • Usher–Hallgren syndrome
  • retinitis pigmentosa–dysacusis syndrome
  • dystrophia retinae dysacusis syndrome

“Usher syndrome is the most common genetic cause of deafblindness, and affects over 400,000 people worldwide.”

“Did you know that Usher syndrome is characterized by hearing loss due to abnormalities in the inner ear (sensorineural hearing loss) and vision loss due to changes in the light sensitive (or photoreceptor) cells in the back of the eye?”

“Usher syndrome is a genetic disease that causes hearing loss, vision loss and sometimes balance problems. Usher syndrome is “recessive” which means that two of the same Usher genes must be inherited - one from the mother, one from the father - in order for the child to have Usher syndrome. Often, parents do not know that they are carriers of the Usher syndrome gene because there is no history of Usher syndrome in the family.

When both parents are carriers, there is a 25% chance that each child will have Usher syndrome. If both parents have the same type of Usher syndrome, all of their children will have Usher syndrome. Some families have several children with Usher syndrome.”

Types of Usher Syndrome and their genetic basis

“Did you know that while there are three types of Usher syndrome and at least 11 USH subtypes, there are hundreds of mutations or variants responsible for Usher syndrome?”

“How many types of Usher syndrome are there?”

Type 1

“Type 1 – causes profound deafness. Vision loss caused by retinitis pigmentosa (RP) may be noticed before the age of 10. Poor balance from birth is often associated with Usher type 1, which causes delays in sitting and walking. Children with Usher type 1 who receive cochlear implants at an early age usually communicate using speech and lip-reading. Many adults with Usher Type 1 communicate with sign language and identify as culturally Deaf and/or DeafBlind.”

“There are five subtypes of Usher 1: types 1B, 1C, 1D, 1F and 1G.”

Type 2

“Type 2 – causes a moderate hearing loss. RP may not become apparent until adolescence. Speech assisted by the use of lip-reading and hearing aids or cochlear implants will usually be their primary method of communication. Balance is not affected, therefore children with Usher Type 2 walk at the typical age of 10 to 14 months.”

Type 2A

USH2A gene

“The USH2A gene provides instructions for making a protein called usherin. Usherin is an important component of basement membranes, which are thin, sheet-like structures that separate and support cells in many tissues. Usherin is found in basement membranes in the inner ear and in the retina, which is the layer of light-sensitive tissue at the back of the eye. Although the function of usherin has not been well established, studies suggest that it is part of a group of proteins (a protein complex) that plays an important role in the development and maintenance of cells in the inner ear and retina. The protein complex may also be involved in the function of synapses, which are junctions between nerve cells where cell-to-cell communication occurs.”

“More than 400 mutations in the USH2A gene have been identified in people with Usher syndrome type II, which is characterized by a combination of hearing loss and vision loss associated with retinitis pigmentosa. Specifically, USH2A gene mutations cause a form of the disorder known as Usher syndrome type IIA (USH2A), which accounts for more than half of all cases of Usher syndrome type II.

Several of these mutations change single amino acids in the usherin protein. These mutations often lead to the production of an abnormally short version of the protein or prevent the cell from making any functional usherin. Other mutations insert or delete small amounts of DNA in the USH2A gene, which probably impairs the normal function of usherin. Researchers have not determined how a missing or altered usherin protein leads to the hearing impairment and vision loss that are characteristic of Usher syndrome type IIA.

It is unclear why some USH2A gene mutations result in Usher syndrome type IIA, while other mutations cause retinitis pigmentosa without hearing loss.”

“The USH2A gene is located on the long arm of chromosome 1 (1q41-q42), which is one of the 23 pairs of chromosomes that contain the genetic material that determines a person’s characteristics, such as their physical appearance and their susceptibility to certain diseases. The USH2A gene is a relatively large gene, containing about 150,000 base pairs of DNA.”

Type 3

“Type 3 – is the rarest form of Usher syndrome. It occurs with higher frequency in individuals of Ashkenazi Jewish and Finnish heritage. Children usually have normal hearing and vision at birth, then develop hearing loss and RP in adolescence or later. Hearing can deteriorate steadily over ten or fifteen years. Some with Usher Type 3 also experience balance problems.”

Type 4

Retinitis Pigmentosa

“Several dozen mutations in the USH2A gene have been reported to cause retinitis pigmentosa, a vision disorder that causes the light-sensing cells of the retina to gradually deteriorate. USH2A gene mutations are the most common cause of the autosomal recessive form of retinitis pigmentosa, accounting for 10 to 15 percent of all cases. This form of the disorder is described as nonsyndromic, which means that it is not associated with other signs and symptoms as part of a genetic syndrome (such as Usher syndrome, described below).

The USH2A gene mutations that cause retinitis pigmentosa change single protein building blocks (amino acids) in the usherin protein. Through a mechanism that is not well understood, these genetic changes lead to the gradual breakdown of specialized light receptor cells called photoreceptors in the retina. A loss of these cells underlies the progressive vision loss characteristic of this condition.”

Management, treatment options, and ongoing research

“We’ve been talking a lot about gene-specific research projects, treatments in development that are specifically tailored to the mutated gene causing the exact Usher subtype that you have. There is also research underway to develop cell-based and cross-cutting therapies. Cross-cutting therapies (e.g. stem cell therapy, neuroprotective gene therapy, optogenetics) have the potential to benefit anyone with Usher syndrome, regardless of their subtype.”

Treatment Options

There are no cure for Usher syndrome or RP but there are assistive technologies which may help. I cover them here.

Ongoing Research

Interventional: Clinical trials that study potential treatments (i.e., drug therapies, procedures, medical devices, etc.)

Observational: Studies that observe and gather information about people without changing or controlling anything. (i.e., natural history studies, patient registries, etc.)

Company Research Target Phase Link
Nanoscope Therapeutics MCO-010 2b Retinitis Pigmentosa News
Frequency Therapeutics FX-322 2 Hearing Loss Clinical Trial
Hadassah Medical Organization “The Effects of Cannabis on Visual Functions in Healthy and Retinitis Pigmentosa Patients” 1 Retinitis Pigmentosa Clinical Trial

“Marijuana May Prevent Blindness In Retinitis Pigmentosa Sufferers”

“The U.S. Food and Drug Administration today approved Luxturna (voretigene neparvovec-rzyl), a new gene therapy, to treat children and adult patients with an inherited form of vision loss that may result in blindness. Luxturna is the first directly administered gene therapy approved in the U.S. that targets a disease caused by mutations in a specific gene.”

End Blindness by 2020

“Stem cells and gene therapy were supposed to revolutionize biomedicine around the turn of the millennium and provide relief for desperate patients with incurable diseases. But for many, progress has been frustratingly slow. We still cannot, for example, regenerate damaged organs like a salamander regrows its tail, and genome engineering is more complicated than cutting and pasting letters in a word document.”

Science is not straightforward. It never goes from A to B to C, it jumps all over. This is why the replication crisis exists. New knowledge cause paradigm shifts in our understanding. An example of this is the Ptolemaic system to Copernican system.

Another problem science faces is funding. Where it’s coming from or lack of it.

It’ll be a while.