Neuronal Ceroid Lipofuscinoses
Patient Information
Characteristics
Background and History
The neuronal ceroid lipofuscinoses or NCLs are a group of inherited neurodegenerative disorders in which defects in enzymes lead to an accumulation of specific molecules in cells leads to degeneration of nerve cells. This group of disorders is considered to be the most common cause of progressive neurological and visual deterioration. Mutations in at least 9 genes have been identified.
Clinical Correlations
There is a wide range in the age of onset. Neurological damage may be evident at birth in some cases whereas the disease is not evident until the 5th and 6th decades in others. At some point in all individuals there is evidence of intellectual and movement (motor) deterioration. Unsteadiness, seizures and loss of vision are usually evident at some point. Eye examinations reveal damage to the optic nerve and dysfunction of the retina is demonstrable by an electroretinogram (ERG). Night blindness, a decrease in side vision, and eventually loss of light perception are important symptoms. The neurological deterioration is relentless and early death eventually follows.
Although the age of onset is a factor in the diagnosis and prognosis, it is necessary to do a gene test to determine which type of NCL is responsible for the clinical picture.
Genetics
Inheritance
Virtually all types of CNLs are inherited in an autosomal recessive pattern although an autosomal dominant pattern can be seen in some families with an adult onset of disease. However, in the majority of families both unaffected parents are carriers of the responsible mutation and disease results when children inherit two copies of the mutation. A gene test is necessary to determine which type of disease is present.
Pedigree
Autosomal dominant
Autosomal dominant disorders require only one mutation for the disease to be expressed. Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease. It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).
Autosomal dominant inheritance leads to a vertical pattern of transmission
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
Diagnosis and Prognosis
The diagnosis usually requires a collaborative effort among pediatricians, pediatric neurologists, and ophthalmologists. The combination of intellectual deterioration, seizures and visual impairment suggest the diagnosis. Brain imaging and tests of retinal function (ERGs) combined with the clinical findings can confirm the clinical impression.
The prognosis is variable and a gene test to determine the specific mutation can be helpful in the determination of prognosis.
Web Resources
Printer Friendly Version: Ctrl/Cmd+P