RESUMO
Crisponi/cold-induced sweating syndrome (CS/CISS) is an autosomal recessive disease characterized by hyperthermia, camptodactyly, feeding and respiratory difficulties often leading to sudden death in the neonatal period. The affected individuals who survived the first critical years of life, develop cold-induced sweating and scoliosis in early childhood. The disease is caused by variants in the CRLF1 or in the CLCF1 gene. Both proteins form a heterodimeric complex that acts on cells expressing the ciliary neurotrophic factor receptor (CNTFR). CS/CISS belongs to the family of "CNTFR-related disorders" showing a similar clinical phenotype. Recently, variants in other genes, including KLHL7, NALCN, MAGEL2 and SCN2A, previously linked to other diseases, have been associated with a CS/CISS-like phenotype. Therefore, retinitis pigmentosa and Bohring-Optiz syndrome-like (KLHL7), Congenital contractures of the limbs and face, hypotonia, and developmental delay syndrome (NALCN), Chitayat-Hall/Schaaf-Yang syndrome (MAGEL2), and early infantile epileptic encephalopathy-11 syndrome (SCN2A) all share an overlapping phenotype with CS/CISS, especially in the neonatal period. This review aims to summarize the existing literature on CS/CISS, focusing on the current state of differential diagnosis, pathogenesis and treatment concepts in order to achieve an accurate and rapid diagnosis. This will improve patient management and enable specific treatments for the affected individuals.
Assuntos
Craniossinostoses/diagnóstico , Citocinas/genética , Deformidades Congênitas da Mão/diagnóstico , Hiperidrose/diagnóstico , Deficiência Intelectual/diagnóstico , Receptores de Citocinas/genética , Trismo/congênito , Subunidade alfa do Receptor do Fator Neutrófico Ciliar/genética , Craniossinostoses/genética , Craniossinostoses/patologia , Morte Súbita/patologia , Diagnóstico Diferencial , Fácies , Deformidades Congênitas da Mão/patologia , Deformidades Congênitas da Mão/terapia , Humanos , Hiperidrose/patologia , Hiperidrose/terapia , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Retinose Pigmentar/diagnóstico , Retinose Pigmentar/genética , Retinose Pigmentar/patologia , Escoliose/diagnóstico , Trismo/diagnóstico , Trismo/patologia , Trismo/terapiaRESUMO
Cytokine receptor like factor 1 (CRLF1) is the gene implicated, when mutated, in Crisponi syndrome/cold-induced sweating syndrome type 1 (CS/CISS1). Here, we report the establishment of induced pluripotent stem cell lines (iPSCs) from fibroblasts of a Turkish CS/CISS1 individual with a homozygous variant in CRLF1 (c.708_709delinsT; p.[Pro238Argfs*6]). This variant is the most frequent variant associated to CS/CISS1 in the Turkish population. These patient derived iPSC lines show all pluripotency markers, a normal karyotype and the ability to differentiate into the three germ layers.
Assuntos
Deformidades Congênitas da Mão , Hiperidrose , Células-Tronco Pluripotentes Induzidas , Fácies , Humanos , SudoreseRESUMO
Crisponi syndrome/cold-induced sweating syndrome type 2 (CS/CISS2) is a rare disease with severe dysfunctions of thermoregulatory processes. CS/CISS2 individuals suffer from recurrent episodes of hyperthermia in the neonatal period and paradoxical sweating at cold ambient temperatures in adolescence. Variants in CLCF1 (cardiotrophin-like-cytokine 1) cause CS/CISS2. Here, we summarize the generation of three clones of one stem cell line (iPSC) of a CS/CISS2 individual carrying the CLCF1 variant c.321C>G on both alleles. These patient derived iPSC clones show a normal karyotype, several pluripotency markers, and the ability to differentiate into the three germ layers.