Batten disease




Batten disease (also known as Spielmeyer-Vogt-Sjögren-Batten disease, CLN3 and JNCL) is an extremely rare and fatal autosomal recessive neurodegenerative disorder that begins in childhood. Batten disease is named after the British pediatrician who first described it in 1903. Also known as Spielmeyer-Vogt-Sjogren-Batten disease, it is the most common form of a group of disorders called the ceroid lipofuscinosis neuronal or CLNs. Although Batten disease originally referred specifically to the juvenile form of CLN (JNCL), the term Batten disease is increasingly used by pediatricians to describe all forms of CLN.

Batten disease and other forms of CLN are relatively rare, occurring in an estimated 2 to 4 of every 100,000 live births in the United States. These disorders appear to be more common in Finland, Sweden, other parts of northern Europe, and Newfoundland, Canada. Although CLNs are classified as rare diseases, they often strike more than one person in families that carry the defective genes.

At least twenty genes have been identified in association with Batten disease, but juvenile NCL, the most prevalent form of Batten disease, has been linked to mutations in the CLN3 gene.


Early symptoms of the disorder usually appear around ages 2–10, with gradual onset of vision problems, or seizures. Early signs may be subtle personality and behavior changes, slow learning or regression, repetitive speech or echolalia, clumsiness, or stumbling. There may be slowing head growth in the infantile form, poor circulation in lower extremities (legs and feet), decreased body fat and muscle mass, curvature of the spine, hyperventilation and/or breath-holding spells, teeth grinding, and constipation.

Over time, affected children suffer mental impairment, worsening seizures, and progressive loss of sight, speech and motor skills. Eventually, children with Batten disease become blind, bedridden, and demented, and die. Batten Disease is a terminal disease; life expectancy varies depending on the type or variation.

Research by the University of Rochester suggests females with juvenile Batten Disease show first symptoms a year later than males, and on average die a year sooner.


CLN3 disease occurs because of disruptions or changes (mutations) of the CLN3 gene located on the short arm (p) of chromosome 16 (16p12.1). The function of the protein encoded by this gene is not yet understood. Researchers suspect that CLN3 disease is caused by alterations within the cell so that the body is unable to break down and recycle substances such as fats, and their associated sugars and proteins in the normal way. Some of these fats, sugars, and proteins then appear to form the lipopigments that accumulate in nerve and other tissue alongside the symptoms associated with this disorder. Although these substances accumulate in most cells, brain cells are affected first.

CLN3 disease is inherited as an autosomal recessive trait. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual inherits one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the altered gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.

Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.


In many instances, Batten disease is initially seen by an optometrist or ophthalmologist during an eye exam because one of the first signs is vision loss. Even though it is also seen in a variety of other diseases as well, a loss of ocular cells should be a warning sign of Batten Disease potentially being present. If Batten disease is a possible diagnosis for an individual, a variety of tests are run to confirm including:

Blood or urine tests.  These tests can detect abnormalities that may indicate Batten disease. For example, elevated levels of a chemical called dolichol are found in the urine of many individuals with CLN. The presence of vacuolated lymphocytes—white blood cells that contain holes or cavities (observed by microscopic analysis of blood smears)—when combined with other findings that indicate CLN, is suggestive for the juvenile form caused by CLN3 mutations.

Skin or tissue sampling. The doctor can examine a small piece of tissue under an electron microscope. The powerful magnification of the microscope helps the doctor spot typical CLN deposits. These deposits are common in skin cells, especially those from sweat glands.

Electroencephalogramme EEG. An EEG uses special patches placed on the scalp to record electrical currents inside the brain. This helps doctors see telltale patterns in the brain's electrical activity that suggest an individual has seizures.

Electrical study of the eyes. These tests, which include visual-evoked responses and electroretinograms, can detect various eye problems common in childhood CLNs.

Computed tomography CT or magnetic resonance imaging MRI. Diagnostic imaging can help doctors look for changes in the brain's appearance. CT uses x-rays and a computer to create a sophisticated picture of the brain's tissues and structures, and may reveal brain areas that are decaying, or “atrophic,” in persons with CLN. MRI uses a combination of magnetic fields and radio waves, instead of radiation, to create a picture of the brain.

Measurement of enzyme activity. Measurement of the activity of palmitoyl-protein thioesterase involved in CLN1, the acid protease involved in CLN2, and, though more rare, cathepsin D activity involved in CLN10, in white blood cells or cultured skin fibroblasts (cells that strengthen skin and give it elasticity) can be used to confirm or rule out these diagnosis.

DNA analysis. If families where the mutation in the gene for CLN3 is known, DNA analysis can be used to confirm the diagnosis or for the prenatal diagnosis of this form of Batten disease. When the mutation is known, DNA analysis can also be used to detect unaffected carriers of this condition for genetic counseling. If a family mutation has not previously been identified or if the common mutations are not present, recent molecular advanced have made it possible to sequence all of the known CLN genes, increasing the chances of finding the responsible mutation(s).


Over time, affected children suffer loss of their sight, mental impairment, worsening seizures, and progressive loss of motor skills. Eventually, those with Batten disease become bedridden, require 24-hour care, and die prematurely


Treatment of manifestations: Treatment is currently symptomatic and palliative only. Seizures, malnutrition, gastroesophageal reflux, pneumonia, sialorrhea, depression and anxiety, spasticity, Parkinsonian symptoms, and dystonia can be effectively managed. Antiepileptic drugs (AEDs) should be selected with caution. Benzodiazepines may help control seizures, anxiety, and spasticity. Trihexyphenydate may improve dystonia and sialorrhea. Individuals with swallowing problems may benefit from placement of a gastric (G) tube.

Surveillance: Routine medical management of children and young adults with complex neurodisability will be relevant to all those affected by CLN, and may include surveillance for swallowing difficulties and recurrent aspiration and radiograph surveillance of hip joints and spine.

Agents/circumstances to avoid: Carbamazepine and phenytoin may increase seizure activity and myoclonus and result in clinical deterioration; lamotrigine may exacerbate seizures and myoclonus.

Genetic counselling: The CLNs are inherited in an autosomal recessive manner with the exception of adult onset, which can be inherited in either an autosomal recessive or an autosomal dominant manner.

Autosomal recessive CLN. The parents of a child with an autosomal recessive form of CLN are obligate heterozygotes, and therefore carry one mutated allele. Heterozygotes have no symptoms. At conception, each sib has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives is possible if the pathogenic variants in the family are known.

Prenatal testing for pregnancies at increased risk is possible if the proband has documented deficient enzyme activity or if the pathogenic variant(s) have been identified in the family.