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Infantile spasms associated with proximal duplication of chromosome 15q
P M Bingham1, N B Spinner, L Sovinsky
1Division of Neurology, Children's Hospital of Philadelphia, Pennsylvania 19104, USA.
Insights
Infantile spasms (IS) in an infant were linked to a rare chromosome abnormality, a supernumerary inverted duplication of chromosome 15. Treatment with ACTH therapy effectively resolved the seizures and EEG abnormalities.
Area of Science:
- Genetics
- Neurology
- Pediatrics
Background:
- Infantile spasms (IS) are a severe epilepsy syndrome in infants.
- Chromosome abnormalities are a known cause of IS, but specific genetic links are still being investigated.
Observation:
- A case of IS is presented in a nondysmorphic infant with mild hypotonia and developmental delay.
- The infant exhibited unilateral sensorineural deafness and torticollis.
- Molecular cytogenetic studies identified a supernumerary inverted duplication of chromosome 15 (inv dup(15)).
Findings:
- This large inv dup(15) was associated with IS and other phenotypic abnormalities.
- ACTH therapy led to prompt seizure remission and normalization of EEG findings.
- This is the second reported case of IS associated with a supernumerary inv dup(15).
Implications:
- The duplicated region on chromosome 15 contains genes for neurotransmitter receptor subunits, suggesting abnormal gene dosage may contribute to seizures.
- Chromosome analysis can aid in diagnosing unexplained infantile spasms.
- Further research into the genetic basis of IS is warranted.
Abstract:
We describe a case of infantile spasms associated with a chromosome abnormality (supernumerary inverted duplication of chromosome 15 [47,XX,+inv dup(15)]). The patient was nondysmorphic and presented with mild hypotonia and delay in acquisition of gross motor milestones before the diagnosis of seizures at age 7 months. Additional features included unilateral sensorineural deafness and torticollis. Molecular cytogenetic studies confirmed that the patient has a large inv dup(15). Inv dup(15) chromosomes are variable with respect to the size and genetic composition of the chromosome and in their phenotypic effects. Patients with small inv dup(15s) may have no phenotypic abnormalities, whereas patients with large inv dup(15s) may have multiple abnormalities. ACTH therapy resulted in prompt remission of seizures and resolution of EEG abnormalities. This is the second report of a patient with IS and a supernumerary inv dup(15). Several genes code for neurotransmitter receptor subunits located in the duplicated region of chromosome 15, and abnormal dosage of these genes may be involved in the genesis of seizure activity in carriers of the inv dup(15). Chromosome analysis may lead to a specific diagnosis in infants with unexplained infantile spasms.