Phenotypic and genotypic features of a pair of Chinese identical twins with congenital insensitivity to pain and anhidrosis

Abstract

Rationale: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive genetic disorder characterized by insensitivity to noxious stimulus and the absence of sweating. Fractures and joint destruction are common complications, but detailed studies on mineral and skeletal homeostasis are not available. Mental retardation is often reported, but detailed observations during childhood are lacking. Patient concerns: A pair of 46-month-old Chinese identical twin brothers was presented at our hospital. The brothers had the typical manifestations of insensitivity to noxious stimulus, inability to sweat, and recurrent episodes of unexplained fever. Fortunately, they did not present common complications such as self-mutilation, trauma, bruise, and repeated bone fractures. Diagnoses: Two novel compound heterozygous variants of NTRK1 (c.632T > A and c.1253_1254delTC) were identified. Interventions: The patients were subjected to routine and specialist clinical examinations. Daily care and symptomatic treatment were given. Outcome: X-ray films of proband 2 showed a fracture in the first metatarsal. Decreased bone mineral density (BMD) and mild-to-moderate retardation of the Gesell developmental schedules (GDS), especially language and adaptability, were observed. Evaluation results for BMD and GDS in proband 2 were worse than those in his brother. Lessons: The current findings expand our knowledge about the spectrum of phenotypic and genotypic features of CIPA, which will help facilitate future genotype–phenotype association studies. Daily care by parents promotes favorable outcomes in patients.

Congenital insensitivity to pain with anhidrosis and multiple Charcot joints in a child: A case report

“…However, a study done on two identical twins with CIPA reported multiple presentations of the twins with indifference to painful stimuli, yet abdominal pain was present, and recurrent episodes of fever of unknown etiology not responsive to antipyretics. [5] Although our patient's mental function was normal, many patients with CIPA develop mental retardation. [1] Innervated sweat glands were reported by one of the studies, but anhidrosis remains predominant.…”

“…[1] Innervated sweat glands were reported by one of the studies, but anhidrosis remains predominant. [2,5] Regarding diagnosis, many studies reported no reaction to pain with having unexplained episodes of hyperpyrexia after birth accompanied by skin dryness. Some studies, including the current case, support the evidence of a delayed diagnosis of CIPA in childhood due to the occurrence of symptoms at a later age.…”

“…There is no standard treatment and surgical reconstruction remains the only invasive intervention in regard to CIPA with joint deformity. [5,6] Those patients are more prone to have multiple infections, most commonly Staphylococcus aureus infection. [5] Orthopedic problems and complications such as autoamputation, self-mutilation, septic arthritis, osteomyelitis, and scoliosis are pretty common.…”

“…[5,6] Those patients are more prone to have multiple infections, most commonly Staphylococcus aureus infection. [5] Orthopedic problems and complications such as autoamputation, self-mutilation, septic arthritis, osteomyelitis, and scoliosis are pretty common. [7] Severe complications have been reported in joint reconstruction surgeries and conservative management with close follow-up is preferred to lower the risk of complications.…”

“…[7] Severe complications have been reported in joint reconstruction surgeries and conservative management with close follow-up is preferred to lower the risk of complications. [5,7] However, progressive scoliosis requires operative intervention, while fracture may be treated conservatively with cast immobilization. Osteomyelitis and septic arthritis are treated accordingly with antibiotics.…”