What are CLN3-related disorders? CLN3-related disorders are a group of conditions that cause vision trouble (retinal degeneration) either by itself or, more commonly, with progressive loss of mental and motor skills. CLN3-related disorders are caused by harmful genetic changes in the CLN3 gene. Symptoms result from a buildup of harmful substances in the cells, which causes damage to the nerves in an individual's brain and body. The two main conditions that make up CLN3-related disorders include neuronal ceroid lipofuscinosis and isolated retinal degeneration. Neuronal ceroid lipofuscinosis, CLN3-related Neuronal ceroid lipofuscinoses (NCL) are a group of inherited diseases that affect an individual’s brain and nerves. Another name for NCL is Batten disease. These conditions lead to blindness, as well as loss of cognitive, speech, and motor skills (developmental regression). There are several forms of NCL caused by harmful genetic changes in different genes. In individuals with CLN3-related NCL, symptoms typically start between the ages of four and ten. Often, the first noticeable symptom is visual impairment that leads to complete blindness within a few years. Learning difficulties, loss of speech and motor skills, behavior problems, and seizures also develop. As individuals get older, they continue to lose skills. By the late teens, most cannot move independently and need help with basic self-care activities. They may also have other symptoms, such as difficulty eating, heart rhythm abnormalities (cardiac dysrhythmia), psychiatric issues, and difficulties with sleep. Due to the age at which symptoms begin, this form of the disorder is often referred to as juvenile NCL. In rare instances, individuals with CLN3-related NCL may have a longer (protracted) disease course, where symptoms begin in childhood but progress at a slower rate. Isolated retinal degeneration, CLN3-related Some individuals with harmful genetic changes in CLN3 have vision trouble without other symptoms (isolated retinal degeneration). In these individuals, the age at which the vision issues start can range from early teens into the forties. Symptoms often begin with difficulty with nighttime vision and progress to legal blindness. How common are CLN3-related disorders? The incidence of all forms of NCL is approximately 1 in 75,000 to 1 in 100,000 births. The exact incidence of NCL caused by CLN3 mutations is unknown, but it is more common among individuals of Scandinavian descent. The incidence of CLN3-related isolated retinal degeneration is unknown. How are CLN3-related disorders treated? There is no treatment for the underlying cause of CLN3-related disorders. For individuals with CLN3-related NCL, treatment is based on the symptoms that are present. Treatment typically includes medications to control seizures and movement problems. Affected individuals may be routinely monitored for swallowing difficulties to determine if a feeding tube would be beneficial. What is the prognosis for an individual with a CLN3-related disorder? The symptoms in individuals with CLN3-related NCL become more severe as they age, and death usually occurs in the late teens or twenties. However, some individuals with the disease have lived into their thirties. Individuals with isolated retinal degeneration experience vision symptoms that progress to legal blindness but are expected to have an average lifespan. Other names forCLN3-related disorders Batten disease CLN3-related neuronal ceroid-lipofuscinosis Neuronal ceroid lipofuscinosis 3 Neuronal ceroid-lipofuscinoses Spielmeyer-Sjogren disease Vogt-Spielmeyer disease References Dragos et al., 2016, Epileptic Disord., 18(S2):73-88, PMID: 27629553 Krantz et al., 2022, Child Care Health Dev., 48(5):842-851, PMID: 35233790 Masten et al., 2021, J Inherit Metab Dis., 44(6):1453-1462, PMID: 34453334 Mirza et al., 2019, Mol Genet Genomic Med., 7(12):e859, PMID: 31568712 OMIM: Online Inheritance in Man, OMIM [204200], 2016, https://www.omim.org/entry/204200 Sleat et al., 2016, Gene., 593(2):284-91, PMID: 27553520 Smirnov et al., 2021, JAMA Ophthalmol., 139(3):278-291, PMID: 33507216 Wright et al., 2020, Ophthalmol Retina, 4(4):433-445, PMID: 31926949