Two Turkish brothers with cold-induced sweating syndrome caused by a novel missense mutation in the CRLF1 gene. B. Tüysüz1, G. YeĊil1, O. Kasapcopur2, PerM. Kanppskog3, H. Boman3 1) Cerrahpasa Pediatric Genetics, Istanbul University, Istanbul, Turkey; 2) Istanbul University, Cerrahpasa Medical Faculty, Department of Rheumatology, Istanbul, Turkey; 3) Center of Medical Genetics and Molecular Medicine Haukeland Hospital, Helse Bergen HF, N-5021 Bergen, Norway.
Cold-induced sweating syndrome is a very rare autosomal recessive disorder characterized by excess sweating induced by cold exposure, reduced pain sensitivity, camptodactyly and kyphoscoliosis. It was initially described by Sohar et al. (Lancet 1978; 312:1073-4) in two Israeli sisters. Knappskog et al. (Am J Hum Genet 2003; 72: 375-83) performed genetic studies, and found out that the Israeli sisters as well as two Norwegian brothers with similar clinical manifestations were homozygous for the mutations in CRLF1 gene. A second locus was also identified in an Australian patient who was compound heterozygous for the mutations in CLFC1 (CISS2) gene on 11q13.3 (Hahn et al., J Neurol Sci 2006; 250: 62-70). Our patients (22 and 13 years old boys) were second and third child of first cousin and healthy parents. Both brothers had excess sweating induced by cold exposure, operated severe dorsal scoliosis, camptodactyly, reduced pain sensitivity, short and smooth tongue and operated cryptorchidism. Their sweating problem and scoliosis were noted at the age of approximately 12 years. Both patient weight, height and head circumference were normal. Older brother had atypical facial features including chubby cheeks, broad nose with anteverted nostrils, short philtrum and bifid uvula. He had also chewing and swallowing problems which were arised in infantile period. His intelligence was normal and he was working as a laboratory staff. However, younger brother had similar facies to his brother but he also had severe mental retardation due to cortical atrophy and history of neonatal hypoxic ischemic encephalopathy. Dorsal severe scoliosis was noted even after the operation. Their electromyelography and blood muscle enzyme levels were normal. We considered cold induced sweating syndrome in these brothers. The coding and flanking regions of all the 8 exons of the CRLF1 gene were amplified, sequenced and the data analyzed mainly as previously described (Knappskog PM et al. Am J Hum Genet 2003; 72:375-83). The patients were homozygous and their parents were heterozygous for a novel missense mutation in CRLF1 c.413CT (p.Pro138Leu). This variant is situated in a predicted (NCBI) EpoR ligand-binding domain. We presented first family with cold induced sweating syndrome from Turkey and fourth family which reported to date. Our patient findings differ from the other reported patients as they have late onset but progressive scoliosis and sweating.