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Abstract Details

Novel Variants and Phenotypic Heterogeneity in Congenital Insensitivity to Pain
Pain
S23 - Pain (1:12 PM-1:24 PM)
002

CIP is a rare disorder. Patients have no perception of pain against injurious stimuli but are otherwise normal. It is caused by loss-of-function mutations in the SCN9A gene encoding for the T voltage-gated sodium channel Nav1.7.

 

 
We present novel variants in the SCN9A gene in three cases with congenital insensitivity to pain (CIP), two of whom were siblings.

Case 1 was an 18 months old male with recurrent self-injurious behavior and insensitivity to pain and heat. Case 2 was a 15 years old male patient with insensitivity to pain, juvenile arthritis, and inability to gain weight. Case 3 (elder sister) had similar complaints. Parents reported insensitivity to pain decreased with time and that both siblings began to experience pain after age 10. All cases had a normal neurologic examination and electromyography (EMG) result, except they were unresponsive to pain.

 

Clinical exome sequencing (CES) from peripheral blood was performed for both cases. Case 1: A homozygous frameshift variant (c.2362dupG (c.2362_2363insG) (p.Asp788GlyfsTer4)) was detected in SCN9A which was predicted as pathogenic in in silico databases. Case 2: A homozygous frameshift variant (c.3143_3154delTCAGTGGTTTTGinsA (p.Ile1048LysfsTer13)) was detected in SCN9A which was predicted as likely pathogenic in in silico databases. Both variants were not reported previously. The segregation analysis was performed for both cases. Case 2 had an additional intronic SNP (rs4303728), which in one study associated this variant with severe postoperative pain.

Homozygous and compound heterozygous mutations cause CIP. Partial regain of pain is a unique situation. The variants can be hypomorphic alleles, allowing low levels of Nav1.7- channel function. The inactivating mutation may have an attenuated effect on channel function. Further studies are required to understand the effect of the variants on Nav1.7 channel function.

Authors/Disclosures
Sinem Seleme Ovunc, MD (University of Michigan)
PRESENTER
Dr. Ovunc has nothing to disclose.
Aysel Kalayci Yigin, PhD Dr. Kalayci Yigin has nothing to disclose.
Betul Kesriklioglu, Jr., MD (Istanbul University) Dr. Kesriklioglu has nothing to disclose.
Gizem Izgi No disclosure on file
Fitnat Ulug No disclosure on file
Sema Saltik No disclosure on file
Mehmet Seven, MD Prof. Seven has nothing to disclose.
Deniz Agirbaslo, MD,PhD (Istanbul University-Cerrahpasa) Dr. Agirbaslo has nothing to disclose.