Abstract
•This cohort reveals a severe HSAN IV phenotype in Jordanian patients.•All patients manifested global developmental delay, microcephaly and poor weight gain.•The most common mutation in our series is (c.1860_1861insT; p.Pro621fs).•A new mutation variant in c.2170 G > A is reported with probably a milder phenotype.
To present the clinical picture, the associated complications and the genetic findings of Jordanian patients diagnosed with Congenital insensitivity to pain with anhidrosis (CIPA).
This is a retrospective study including 7 patients diagnosed with CIPA presenting to Jordan University Hospital neurology clinic between 2001 and 2017.
Among five families, seven patients were diagnose with CIPA and followed for a period ranging from one month to 6 years.
The initial symptom observed in all patients was high fever in the first few days after birth, decreased sensation to pain and decreased sweating were later noted. Poor weight gain, microcephaly and global developmental delay were present in most cases. All patients had tongue ulcerations. Fingers/toes ulcerations were present in 6/7 (86.0 %), hip joint dislocation in 3/7 (43.0 %), chronic arthritis and joint swelling in 6/7 (86.0 %), corneal ulcers in 4/7 (57.1 %) and kidney amyloidosis in 1/7 (13.0 %) of all patients. Death occurred in 4/7 (57.1 %) patients.
Consanguinity was present in all families. Mutation analysis revealed three variants in NTRK1 gene. The frameshift (c.1860_1861insT; p.Pro621fs) mutation was common in our series. One patient carried a novel missense mutation (c.2170 G > A; p.Gly724Ser). The third missense mutation (C2125 G > T; p.Val709Leu) was reported in a previous study in one patient.
This cohort reveals a severe CIPA phenotype necessitating thorough multidisciplinary care and follow up.