Labour outcomes in siblings with channelopathy associated insensitivity to pain due to bi-alleleic SCN9A mutations

Abstract

The gene SCN9A encodes for the voltage-gated sodium channel Nav1.7, which is highly expressed in pain sensing neurons. Bi-allelic ‘loss of function’ mutations result in a channelopathy associated with insensitivity to pain and anosmia. This is the first report of the labour and postpartum outcomes of two sisters who belong to a non-consanguineous Caucasian family with homozygous SCN9A mutations. Neither sister experienced pain during labour; this had major implications for the staff titrating the syntocinon for labour augmentation and contributed towards their ultimate delivery by caesarean section. During the postpartum period, one of the sisters developed lower limb sensory loss and investigations revealed a spinal haematoma and unrecognized bilateral pelvic fractures. The other sister had an uneventful recovery and both babies are well. These case histories underline the importance of pain in labour management and its function in alerting patients and staff to problems during the puerperium.

Human Labor Pain Is Influenced by the Voltage-Gated Potassium Channel KV6.4 Subunit

“…Hence, the phenotype for less painful labor was defined operationally as nulliparous parturients who did not request nor use epidural, inhalational or opioid-based analgesia. This behavioral definition would have captured individuals with SCN9A channelopathy who reported entirely painless labor (Haestier et al, 2012). The studies commenced in October 2012 after National Research Ethics Service and Human Research Authority approval (Reference: 12-EE-0369) was granted.…”

“…Although there are well-established ethnic, social, and cultural factors that influence the experience and expression of pain during labor ( Whitburn et al., 2017 ), broader genetic effects on labor pain may also exist. For example, women with the very rare Mendelian disorder congenital insensitivity to pain due to bi-allelic non-functional mutations in SCN9A (MIM: 243000 ) do not report labor pain or require analgesics during labor ( Haestier et al., 2012 ). SCN9A encodes for the voltage-gated sodium channel Na V 1.7, expressed selectively in nociceptive and autonomic neurons, and mutations in SCN9A have well-documented roles in causing extremely painful or painless phenotypes ( Bennett et al., 2019 ).…”