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Contiguous deletion of KCNQ2 and CHRNA4 may cause a different disorder from benign familial neonatal seizures.

Pascual FT, Wierenga KJ, Ng YT - Epilepsy Behav Case Rep (2013)

Bottom Line: All were developmentally delayed.None presented with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) phenotype associated with CHRNA4 mutation.This study supports reports of KCNQ2 and CHRNA4 deletions associated with phenotypes different from typical BFNS.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

ABSTRACT
Benign familial neonatal seizures (BFNS) is an autosomal dominant disorder associated with heterozygous mutations of either the KCNQ2 or KCNQ3 gene. Most cases have mutations of the KCNQ2 gene. A handful of cases with KCNQ2 and CHRNA4 deletions have been identified with different phenotypic presentations. Only two cases presented with typical BFNS features. Benign familial neonatal seizures is associated with normal exam and work-up, and seizure remission is seen in the first month of life. We report three unrelated individuals with KCNQ2 and CHRNA4 deletions, presenting with neonatal seizures and developmental delay. Their seizures started within one week after birth; all required antiepileptic drugs. Each had normal brain magnetic resonance imaging and at least two electroencephalograms with either normal or abnormal findings. All were developmentally delayed. None presented with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) phenotype associated with CHRNA4 mutation. This study supports reports of KCNQ2 and CHRNA4 deletions associated with phenotypes different from typical BFNS.

No MeSH data available.


Related in: MedlinePlus

Chromosomal location of the microdeletions on 20q13.33. The size of contiguous chromosomal deletion for the three patients is depicted below the stylized chromosome. Further below is a cartoon of the genes mapping to the deleted region. The segment between the vertical dashed bars represents the contiguous deletion seen in patients 1 and 2, while the entire depicted segment represents the deletion seen in patient 3.
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f0010: Chromosomal location of the microdeletions on 20q13.33. The size of contiguous chromosomal deletion for the three patients is depicted below the stylized chromosome. Further below is a cartoon of the genes mapping to the deleted region. The segment between the vertical dashed bars represents the contiguous deletion seen in patients 1 and 2, while the entire depicted segment represents the deletion seen in patient 3.

Mentions: A 10-month-old Mexican-American male was born at term, following induced labor due to oligohydramnios. Pregnancy was complicated by uterine fibroids, depression, and exposure to alcohol, marijuana, and cigarette smoking. He was a product of nonconsanguineous parents. At birth, he had normal APGAR scores and physical exam. On postnatal day seven, he started having several seizures daily, associated with head turning to the left, followed by secondary generalization for 15 to 30 s. Metabolic work-up was unrevealing, except for elevated thyroid stimulating hormone with normal free thyroxine. Brain magnetic resonance imaging (MRI) was normal. His first electroencephalogram (EEG) was normal. Repeat EEG a few days later showed excessive sharp transients with intermittent high voltage slowing. Monotherapy with levetiracetam failed to control his seizures. Oxcarbazepine was added, which stopped his seizures at age one month. At age three months, he had a seizure while off all AEDs. A subsequent EEG was normal. At six months, he was noted to have mild developmental delay. He had a seizure with fever after vaccination at six months. His mother had febrile seizures as a child, and a second-degree paternal uncle had seizures until age two years. No one else had seizures in the family (pedigree shown in Fig. 1-A). The patient's genetic testing showed a 521-kb deletion on 20q13.33 involving 22 genes (11 OMIM genes), including KCNQ2 and CHRNA4 (Fig. 2). Family members declined to undergo genetic testing.


Contiguous deletion of KCNQ2 and CHRNA4 may cause a different disorder from benign familial neonatal seizures.

Pascual FT, Wierenga KJ, Ng YT - Epilepsy Behav Case Rep (2013)

Chromosomal location of the microdeletions on 20q13.33. The size of contiguous chromosomal deletion for the three patients is depicted below the stylized chromosome. Further below is a cartoon of the genes mapping to the deleted region. The segment between the vertical dashed bars represents the contiguous deletion seen in patients 1 and 2, while the entire depicted segment represents the deletion seen in patient 3.
© Copyright Policy - CC BY-NC-SA
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150641&req=5

f0010: Chromosomal location of the microdeletions on 20q13.33. The size of contiguous chromosomal deletion for the three patients is depicted below the stylized chromosome. Further below is a cartoon of the genes mapping to the deleted region. The segment between the vertical dashed bars represents the contiguous deletion seen in patients 1 and 2, while the entire depicted segment represents the deletion seen in patient 3.
Mentions: A 10-month-old Mexican-American male was born at term, following induced labor due to oligohydramnios. Pregnancy was complicated by uterine fibroids, depression, and exposure to alcohol, marijuana, and cigarette smoking. He was a product of nonconsanguineous parents. At birth, he had normal APGAR scores and physical exam. On postnatal day seven, he started having several seizures daily, associated with head turning to the left, followed by secondary generalization for 15 to 30 s. Metabolic work-up was unrevealing, except for elevated thyroid stimulating hormone with normal free thyroxine. Brain magnetic resonance imaging (MRI) was normal. His first electroencephalogram (EEG) was normal. Repeat EEG a few days later showed excessive sharp transients with intermittent high voltage slowing. Monotherapy with levetiracetam failed to control his seizures. Oxcarbazepine was added, which stopped his seizures at age one month. At age three months, he had a seizure while off all AEDs. A subsequent EEG was normal. At six months, he was noted to have mild developmental delay. He had a seizure with fever after vaccination at six months. His mother had febrile seizures as a child, and a second-degree paternal uncle had seizures until age two years. No one else had seizures in the family (pedigree shown in Fig. 1-A). The patient's genetic testing showed a 521-kb deletion on 20q13.33 involving 22 genes (11 OMIM genes), including KCNQ2 and CHRNA4 (Fig. 2). Family members declined to undergo genetic testing.

Bottom Line: All were developmentally delayed.None presented with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) phenotype associated with CHRNA4 mutation.This study supports reports of KCNQ2 and CHRNA4 deletions associated with phenotypes different from typical BFNS.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

ABSTRACT
Benign familial neonatal seizures (BFNS) is an autosomal dominant disorder associated with heterozygous mutations of either the KCNQ2 or KCNQ3 gene. Most cases have mutations of the KCNQ2 gene. A handful of cases with KCNQ2 and CHRNA4 deletions have been identified with different phenotypic presentations. Only two cases presented with typical BFNS features. Benign familial neonatal seizures is associated with normal exam and work-up, and seizure remission is seen in the first month of life. We report three unrelated individuals with KCNQ2 and CHRNA4 deletions, presenting with neonatal seizures and developmental delay. Their seizures started within one week after birth; all required antiepileptic drugs. Each had normal brain magnetic resonance imaging and at least two electroencephalograms with either normal or abnormal findings. All were developmentally delayed. None presented with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) phenotype associated with CHRNA4 mutation. This study supports reports of KCNQ2 and CHRNA4 deletions associated with phenotypes different from typical BFNS.

No MeSH data available.


Related in: MedlinePlus