KCNQ2-Related Disorders

Summary

KCNQ2-related disorders are a group of epileptic diseases that start during the first 4 weeks of a child's life (neonatal period). The groups is made up of various different diseases whose signs and symptoms vary. The conditions range from the less severe form KCNQ2-related benign familial neonatal epilepsy (KCNQ2-BFNE) to the more severe form KCNQ2-related epileptic encephalopathy (KCNQ2-NEE).

Cause

These disorders are caused by mutations in the KCNQ2 gene.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

Inheritance is autosomal dominant.

Signs and symptoms

KCNQ2-BFNE is characterized by seizures that start in otherwise healthy infants around day 3 of life and usually go away within 1 to 4 months. KCNQ2-NEE is characterized by epilepsy and profound intellectual disability and seizures that begin in the first weeks of life and typically show little response to treatment.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 100% of people have these symptoms

• Intellectual disability(Mental deficiency)

80%-99% of people have these symptoms

• EEG with burst suppression
• Epileptic encephalopathy
• Generalized tonic seizure

30%-79% of people have these symptoms

• Abnormal globus pallidus morphology
• Apnea
• Cerebral edema(Swelling of brain)
• Dystonia
• Epileptic spasm
• Facial erythema(Blushed cheeks)
• Feeding difficulties(Feeding problems)
• Inability to walk
• Muscular hypotonia(Low or weak muscle tone)
• Pallor
• Poor gross motor coordination
• Profound global developmental delay

5%-29% of people have these symptoms

• Cerebral atrophy(Degeneration of cerebrum)
• Febrile seizure (within the age range of 3 months to 6 years)(Fever induced seizures)
• Global developmental delay
• Hypoplasia of the corpus callosum(Underdevelopment of part of brain called corpus callosum)
• Hypsarrhythmia
• Motor delay

Diagnosis

The diagnosis is based on the presence of characteristic clinical findings and heterozygous pathogenic variants in KCNQ2 , which codes for voltage-gated potassium channel subunits.<ref>Miceli F, Soldovieri MV, Joshi N, et al. KCNQ2-Related Disorders. 2010 Apr 27 [Updated 2018 Sep 27]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK32534/ </ref>[1].

In KCNQ2-BFNE, all laboratory tests are normal, including brain CT and MRI. In KCNQ2-NEE, brain MRI frequently shows bilateral or asymmetric hyperintensities in the basal ganglia, and sometimes in the thalamus; these may resolve over time. Other common findings are small frontal lobes with increased adjacent extra-axial spaces, thin corpus callosum, and decreased posterior white matter volume.

Treatment

KCNQ2-BFNE.

• The majority of children can be kept seizure-free by using phenobarbital (20 mg/kg as loading dose and 5 mg/kg/day as maintenance dose).
• In some affected individuals, seizures require other antiepileptic drugs (AEDs).

KCNQ2-NEE. Children have multiple daily seizures resistant at onset to phenobarbital and other common old- and new-generation AEDs, alone or in combination. Sodium channel blockers like phenytoin (PHT) or carbamazepine (CBZ) were shown to control seizures in several patients and should be considered first-line treatment.<ref>Miceli F, Soldovieri MV, Joshi N, et al. KCNQ2-Related Disorders. 2010 Apr 27 [Updated 2018 Sep 27]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK32534/ </ref>[2].

References

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NIH genetic and rare disease info

• NIH info on KCNQ2-Related Disorders

KCNQ2-Related Disorders is a rare disease.

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