Congenital insensitivity to pain with anhidrosis (CIPA), also known as hereditary sensory and autonomic neuropathy type IV, is a condition which affects the nervous system. From birth, affected individuals never feel pain in any part of their body when injured. The condition manifests itself as pseudohermaphroditism, hypergonadotropic hypogonadism, reduced or absent puberty, and infertility. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. 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. SCN manifests in infancy with life-threatening bacterial infections. This is a retrospective study including 7 patients diagnosed with CIPA presenting to Jordan University Hospital neurology clinic between 2001 and 2017. Congenital insensitivity to pain with anhidrosis or CIPA is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Congenital insensitivity to pain with anhidrosis is an autosomal recessive hereditary disorder characterized by recurrent episodic fever, anhidrosis (inability to sweat), absence of reaction to noxious stimuli, self‐mutilating behavior, and mental retardation. Myotonia congenita is a congenital neuromuscular channelopathy that affects skeletal muscles. Hereditary inclusion body myopathies (HIBM) are a group of rare genetic disorders which have different symptoms. Poor weight gain, microcephaly and global developmental delay were present in most cases. The conditions described here are separate from the HSAN group of disorders, which have more specific signs and cause. It is also sometimes referred to as hereditary sensory and autonomic neuropathy type IV (HSAN4). Cognitive disorders are commonly coincident. Congenital myopathies account for one of the top neuromuscular disorders in the world today, comprising approximately 6 in 100,000 live births every year. [ citation needed ], It is caused by a mutation in NTRK1, a gene encoding the neurotrophic tyrosine kinase receptor. ScienceDirect ® is a registered trademark of Elsevier B.V. ScienceDirect ® is a registered trademark of Elsevier B.V. Congenital insensitivity to pain with anhidrosis syndrome: A series from Jordan. They are a group of heterogeneous disorders characterized by muscle weakness which is present at birth and the different changes on muscle biopsy that ranges from myopathic to overtly dystrophic due to the age at which the biopsy takes place. Burn injuries are among the more common injuries. To present the clinical picture, the associated complications and the genetic findings of Jordanian patients diagnosed with Congenital insensitivity to pain with anhidrosis (CIPA). Among five families, seven patients were diagnose with CIPA and followed for a period ranging from one month to 6 years. This pathology is caused by a genetic mutation in the NTRK1 gene, which encodes a tyrosine receptor (TrkA) for nerve growth factor (NGF). Amira Masri and Mohammad Shboul contributed equally to the manuscript. Hereditary inclusion body myopathies comprise both autosomal recessive and autosomal dominant muscle disorders that have a variable expression (phenotype) in individuals, but all share similar structural features in the muscles. Because people with this condition are unable to sweat, they are unable to regulate their body temperature. The hallmark of the disease is the failure of initiated contraction to terminate, often referred to as delayed relaxation of the muscles (myotonia) and rigidity. Of note, myotonia congenita has no association with malignant hyperthermia (MH). [5], Mitochondrial abnormalities in muscle cells have been found in people with CIPA. People with homozygous mutations of the PRDM12 gene experience congenital insensitivity to pain (CIP). Methods. This cohort reveals a severe CIPA phenotype necessitating thorough multidisciplinary care and follow up. [2] Approximately 20% of people with CIPA die of hyperthermia by age 3. Rivka Carmi is an Israeli pediatrician and geneticist. A 10 year-old male patient presented to the pediatric emergency department with fever, ulcers on the skin which did not heal and erythema on the left amputated extremity. Congenital insensitivity to pain with anhidrosis (CIPA) is a genetic condition with two characteristic features – the inability to feel pain and temperature and a significant lack of sweating. All patients had tongue ulcerations. Skin biopsies show a lack of innervation of the eccrine glands [2] and nerve biopsies show a lack of small myelinated and unmyelinated fibers. PR domain zinc finger protein 12 is a protein that in humans is encoded by the PRDM12 gene. With no pain sensation, the aches and pains that accompany accidents, medical procedures and aging simply wouldn't exist. Because feeling physical pain is vital for survival, CIP is an extremely dangerous condition. Hereditary motor and sensory neuropathies (HMSN) is a name sometimes given to a group of different neuropathies which are all characterized by their impact upon both afferent and efferent neural communication. His right knee and right ankle are enlarged and distorted. She served as President of Ben-Gurion University of the Negev (BGU) in May 2006-December 2018. One patient carried a novel missense mutation (c.2170 G > A; p.Gly724Ser). Pain is your body's way of telling you something is wrong. This article uses CIP broadly to describe features common to all H… A case of a male patient presenting with loss of pain and temperature sensation, lack of sweat, and mild mental retardation is described. A life free of pain is actually quite dangerous, however. Congenital insensitivity to pain with anhidrosis (CIPA) is a rare disease classified as hereditary sensory and auto-nomic neuropathy (HSAN) type IV [1, 2] according to Dyck et al. Enzymes target gene promoters in order to control gene expression. Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive disorder of the nervous system which prevents the feeling of pain or temperature, and prevents a person from sweating. Corneal ulceration occurs due to lack of protective impulses. The patients present in early childhood with frequent episodes of fever and absence of sweating. Congenital insensitivity to pain and anhidrosis (CIPA) is a rare disorder affecting autonomic nervous system, and therefore has been described as Hereditary Sensory and Autonomic Neuropathies (HSAN). This cohort reveals a severe HSAN IV phenotype in Jordanian patients. Severe congenital neutropenia (SCN), also often known as Kostmann syndrome or disease, is a group of rare disorders that affect myelopoiesis, causing a congenital form of neutropenia, usually without other physical malformations. [4] NTRK1 is a receptor for nerve growth factor (NGF). Familial dysautonomia (FD) is a rare, progressive, recessive genetic disorder of the autonomic nervous system seen primarily in people of Eastern European Jewish descent that affects the development and survival of sensory, sympathetic and some parasympathetic neurons in the autonomic and sensory nervous system. Congenital insensitivity to pain with anhidrosis (CIPA) also known as hereditary … [ citation needed ], Lack of pain puts those with CIPA at a high risk for accidental self-mutilation. The consultation of a child female in our center with CIPA and a tibia fracture in pseudoarthro… The … [2]. Congenital insensitivity to pain with anhidrosis is a rare autosomal recessive disorder caused by pathogenic variants in the gene NTRK1. A new mutation variant in c.2170 G > A is reported with probably a milder phenotype. Congenital insensitivity to pain with anhidrosis (CIPA) has two characteristic features: the inability to feel pain and temperature, and decreased or absent sweating (anhidrosis). Hereditary sensory and autonomic neuropathy type I or hereditary sensory neuropathy type I is a group of autosomal dominant inherited neurological diseases that affect the peripheral nervous system particularly on the sensory and autonomic functions. This enzyme catalyzes the biodegradation of fatty acid derivatives known as gangliosides. The autonomic disturbances, if present, manifest as sweating abnormalities. Complications can include muscle breakdown and high blood potassium. Congenital insensitivity to pain with anhidrosis is a rare disease with an autosomal recessive inheritance. https://doi.org/10.1016/j.clineuro.2019.105636. 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