CLN7 disease is an inherited disorder that primarily affects the nervous system. The signs and symptoms of this condition typically begin between ages 2 and 7. The initial features are usually vision loss and problems with movement that might seem like clumsiness. Additional signs and symptoms of CLN7 disease include muscle twitches (myoclonus), difficulty coordinating movements (ataxia), recurrent seizures (epilepsy), and speech impairment. Mental functioning and motor skills (such as sitting and walking) decline with age. Individuals with CLN7 disease typically do not survive past their teens.

CLN7 disease is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs), which may also be collectively referred to as Batten disease. All these disorders affect the nervous system and typically cause worsening problems with vision, movement, and thinking ability. The different NCLs are distinguished by their genetic cause. Each disease type is given the designation "CLN," meaning ceroid lipofuscinosis, neuronal, and then a number to indicate its subtype.

Mutations in the MFSD8 gene cause CLN7 disease. The MFSD8 gene provides instructions for making a protein whose function is unknown. The MFSD8 protein is embedded in the membrane of cell compartments called lysosomes, which digest and recycle different types of molecules. Based on the structure of the protein, MFSD8 probably transports molecules across the lysosomal membrane, but the specific molecules it moves have not been identified.

MFSD8 gene mutations likely lead to the production of a protein with altered structure or function. It is unclear how an altered MFSD8 protein leads to the severe neurological features of CLN7 disease. CLN7 disease, like other NCLs, is characterized by the accumulation of proteins and other substances in lysosomes. These accumulations occur in cells throughout the body; however, nerve cells seem to be particularly vulnerable to their effects. These accumulations can cause cell damage leading to cell death. Individuals with CLN7 disease have gradual nerve cell loss in certain parts of the brain, which likely leads to the signs and symptoms of this condition.

Normal Function

The MFSD8 gene provides instructions for making a protein whose function is unknown. The MFSD8 protein is embedded in the membrane of cell compartments called lysosomes, which digest and recycle different types of molecules. It is one of a large group of related proteins called the major facilitator superfamily of secondary active transporter proteins. Proteins in this family move certain molecules within a cell or in and out of cells. While it is likely that the MFSD8 protein transports molecules across the lysosomal membrane, the specific molecules it moves have not been identified.

Health Conditions Related to Genetic Changes

CLN7 disease

At least 30 mutations in the MFSD8 gene have been found to cause CLN7 disease. This condition typically starts in early childhood with the loss of previously acquired skills (developmental regression), recurrent seizures (epilepsy), muscle twitches (myoclonus), difficulty coordinating movements (ataxia), speech impairment, and vision loss. Mental functioning and motor skills (such as sitting and walking) decline with age. Individuals with CLN7 disease typically do not survive past their teens.

MFSD8 gene mutations that cause CLN7 disease likely lead to the production of a protein with altered structure or function. One MFSD8 gene mutation is responsible for almost all cases of CLN7 disease in the Roma population of the Czech Republic. This mutation replaces the protein building block (amino acid) threonine with the amino acid lysine at position 294 in the MFSD8 protein (written as T294K). A variety of other mutations cause the condition in other populations.

It is unclear how an altered MFSD8 protein leads to the severe neurological features of CLN7 disease. CLN7 disease is characterized by the accumulation of proteins and other substances in lysosomes. These accumulations occur in cells throughout the body; however, nerve cells seem to be particularly vulnerable to their effects. These accumulations can cause cell damage leading to cell death. Individuals with CLN7 disease have gradual nerve cell loss in certain parts of the brain, which likely leads to the signs and symptoms of this condition.

Other Names for This Gene

• ceroid-lipofuscinosis neuronal protein 7
• CLN7
• major facilitator superfamily domain-containing protein 8
• MFSD8_HUMAN
• MGC33302

Genomic Location

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

The incidence of CLN7 disease is unknown; more than 70 cases have been described in the scientific literature. CLN7 disease was first diagnosed in the Turkish population and was thought to be limited to individuals in that group. However, CLN7 disease has now been identified in people around the world. Collectively, all forms of NCL affect an estimated 1 in 100,000 individuals worldwide.