A new case series of Crisponi syndrome in a Turkish family and review of the literature

Abstract

Crisponi syndrome/cold-induced sweating syndrome (CS/CISS) is a rare autosomal recessive disorder with a complex phenotype, reported in the neonatal period for CS and in the evolutive one for CISS. The syndrome usually manifests at birth. The aim of this study was to report on three new patients with CS and review the Turkish patients. We report here on three patients from two related families harboring a homozygous mutation in the cytokine receptor-like factor-1 (CRLF1) gene. DNA samples of the three patients and their parents were subjected to a mutational analysis of the CRLF1 gene at the Institute of Biomedical and Genetic Research - National Research Council, Cagliari (Italy). Direct sequencing of the nine coding exons and surrounding intronic regions of CRLF1 was performed using specific primers. All three patients were found to be homozygotes for the mutation c.708_709delinsT, which leads to a frameshift in the second fibronectin type III domain (p.Pro238Argfs*6). CS should be considered in the differential diagnosis of newborns with muscle contractions, feeding and swallowing difficulties, dysmorphic facial findings, camptodactyly, and hypertermia. Neonatologists must be aware of this syndrome that, although very rare worldwide, has a higher prevalence in Turkey.

Clinical and molecular genetic findings of Crisponi/cold‐induced sweating syndrome (CS/CISS) spectrum in patients from Turkey

“…The proportion of reported cases of Turkish origin with CRLF1 ‐related CS/CISS increased from 26.5% (26/88) to 42% (45/107) with the addition of our cohort, approaching almost half of the reported cases. The most common CRLF1 allele was c.708_709delCCinsT, identified in 10 families from Mardin province, suggesting that this alteration originates from a founder effect 3,8,26,27 . The c.983dupG variant we detected in two unrelated families from Mardin, was previously reported from Saudi Arabia 28,29 .…”

“…suggesting that this alteration originates from a founder effect. 3,8,26,27 The c.983dupG variant we detected in two unrelated families from Mardin, was previously reported from Saudi Arabia. 28,29 All patients harboring the c.776C>A variant, including the two unrelated patients reported herein, were also of Turkish origin.…”

Crisponi/cold‐induced sweating syndrome: Differential diagnosis, pathogenesis and treatment concepts

“…Most CS/CISS1 individuals originate from Europe, especially from the Mediterranean region [Italy mainland (4) and Sardinia (12 + 15 not tested for variants in CRLF1 ), Turkey (23), Spain (8), Lybia (3) and France (2)]. Others are from the Saudi Arabia (13), India, Pakistan, Japan, Australia, North or Central America . Although most of the disease‐associated CRLF1 variants are private and found only in single families, some variants occur frequently in distinct CS/CISS1 individuals from a specific geographical region (eg, c.226T>G and c.676_677dupA in Sardinia, c.708_709delinsT in Turkey, c.983dupG in Saudi Arabia and c.713dupC in Spain, Turkey, Roma population).…”

“…Up to now, 37 disease causing CRLF1 variants in 73 patients from 53 families have been reported in the medical literature. 4,[7][8][9][10]12,[17][18][19][20][21][22][23][24][25][26][27][28][29][30] In total, 88 CS/CISS1 individuals were identified, although 15 Sardinian CS/CISS1 individuals were not genetically analyzed because they died before CRLF1 had been found to be associated with the disease. 1 Table 1, we report here three novel variants in 3 of…”