Autosomal dominant early childhood seizures associated with chondrocalcinosis and a mutation in the ANKH Gene.
We describe the pattern of early childhood seizures within a family with autosomal dominant chondrocalcinosis (CCAL, which causes adult-onset arthritis). All affected family members with CCAL experienced seizures in early childhood, usually, but not always, associated with fever. Similarities exist to the syndrome of generalized epilepsy with febrile seizures plus (GEFS+). A mutation within the ANKH gene on chromosome 5p has been found previously in this family; other patients with familial CCAL (but without seizures) have mutations in the same gene. ANKH codes for a transmembrane protein involved in the regulation of extracellular pyrophosphate ion levels, although its precise mechanism of action remains unclear. It is highly expressed in the brain, and its expression may be influenced by seizure activity. The mutation within this family creates a premature initiation codon, adding four amino acids to the N-terminus of the protein. We postulate that this may lead to a gain of function, causing seizure susceptibility as well as chondrocalcinosis. Mutations within this gene may underlie other forms of genetic epilepsy and febrile seizures.
McKee
Shane
S
Northern Ireland Regional Genetics Service, Belfast City Hospital, Belfast, United Kingdom. shanemckee@doctors.org.uk
Pendleton
Adrian
A
Dixey
Josh
J
Doherty
Michael
M
Hughes
Anne
A
D001168:Arthritis / Q000235:genetics*; D002675:Child, Preschool; D002805:Chondrocalcinosis / Q000235:genetics*; D018387:Codon, Initiator / Q000235:genetics; D011756:Diphosphates / Q000378:metabolism; D004829:Epilepsy, Generalized / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D028061:Phosphate Transport Proteins; D012640:Seizures / Q000235:genetics*; D003294:Seizures, Febrile / Q000235:genetics
C498770:ANKH protein, human; D018387:Codon, Initiator; D011756:Diphosphates; D008565:Membrane Proteins; D028061:Phosphate Transport Proteins