2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-CIPA presented as Fever of Unknown Origin in a patient with a novel variant in<em> NTRK1</em>

Pdf Summary

Congenital Insensitivity to Pain with Anhidrosis (CIPA), also known as Hereditary Sensory and Autonomic Neuropathy type 4 (HSAN4), is a rare autosomal recessive disease characterized by the loss of pain sensation. It is caused by biallelic pathogenic variants in the NTRK1 gene. Symptoms of CIPA include self-mutilating behavior, corneal ulcerations, joint injuries, and anhidrosis leading to episodic hyperthermia. This case report describes the first confirmed Mexican patient with CIPA, who initially presented with Fever of Unknown Origin (FUO) and was later diagnosed with the disease. The patient also exhibited delayed milestones, growth abnormalities, and microcephaly.<br /><br />Early diagnosis of CIPA is important to prevent complications associated with pain insensitivity, such as self-harm. In this case, the genetics perspective led to an early diagnosis, allowing for timely intervention and comprehensive care. The patient's fever was managed through physical treatments and cooling the environment. An NGS panel for neuropathies was performed, which revealed two pathogenic variants in the NTRK1 gene. Family testing confirmed that the variants were in trans and diagnosed the patient with compound heterozygosity.<br /><br />The clinical manifestations of the patient were compared with the literature, showing similar patterns of recurrent fever, intellectual disability, and self-mutilation. Corneal ulcerations and Charcot's arthropathy were also observed in other cases. Notably, the novel variant identified in this patient highlights the contribution of Latin American ancestry to CIPA.<br /><br />Overall, early diagnosis of CIPA allows for appropriate management and potentially better outcomes for patients. Continued research and genetic testing can further improve our understanding of this rare disease and its variants.

Asset Subtitle

Presenting Author - Karla Cifuentes-Uribe, MD; Co-Author - Alejandra Reyes-De La Rosa, MD; Co-Author - America Villasenor-Dominguez, MD; Co-Author - Rodrigo Moreno-Salgado, MD;

Meta Tag

Clinical History

Cognitive Disorders

Etiology

Genetic Testing

Inheritance Patterns

Intellectual disability

Natural History

NextGen Sequencing

Co-Author Alejandra Reyes-De La Rosa, MD

Co-Author America Villasenor-Dominguez, MD

Co-Author Rodrigo Moreno-Salgado, MD

Presenting Author Karla Cifuentes-Uribe, MD

Keywords

Congenital Insensitivity to Pain with Anhidrosis

CIPA

Hereditary Sensory and Autonomic Neuropathy type 4

HSAN4

NTRK1 gene

self-mutilating behavior

anhidrosis

episodic hyperthermia

Fever of Unknown Origin

genetic testing