Cold-induced sweating syndrome is an autosomal recessive disorder characterized in the neonatal period by orofacial weakness with impaired sucking and swallowing resulting in poor feeding necessitating medical intervention. Affected infants show a tendency to startle, with contractions of ... Cold-induced sweating syndrome is an autosomal recessive disorder characterized in the neonatal period by orofacial weakness with impaired sucking and swallowing resulting in poor feeding necessitating medical intervention. Affected infants show a tendency to startle, with contractions of the facial muscles in response to tactile stimuli or during crying, trismus, abundant salivation, and opisthotonus. During the first year, most infants have spiking fevers. These features, referred to as 'Crisponi syndrome' in infancy, can result in early death without advanced care. After the first 2 years, the abnormal muscle contractions and fevers abate, and most patients show normal psychomotor development. From childhood onward, the most disabling symptoms stem from impaired thermoregulation and disabling abnormal sweating, which can be treated with clonidine. Patients have hyperhidrosis, mainly of the upper body, in response to cold temperatures, and sweat very little with heat. Other features include characteristic facial anomalies, such as round face, chubby cheeks, micrognathia, high-arched palate, low-set ears, and depressed nasal bridge, dental decay, camptodactyly, and progressive kyphoscoliosis (summary by Hahn et al., 2010). Cold-induced sweating syndrome-1 (CISS1; 272430), caused by mutation in the CRLF1 gene (604237), is a clinically indistinguishable disorder.
Rousseau et al. (2006) reported an Australian man, first examined when he was 46 years of age, who stated that he had feeding difficulties as an infant and suffered all his life from profuse sweating on the face, ... Rousseau et al. (2006) reported an Australian man, first examined when he was 46 years of age, who stated that he had feeding difficulties as an infant and suffered all his life from profuse sweating on the face, trunk, and upper limbs when cold in addition to inability to sweat in hot weather. Thermoregulatory sweat tests confirmed the paradoxical sweating response; detailed autonomic studies revealed no other abnormalities. There was no family history of the condition and no parental consanguinity; his sister, 4 children, and grandchildren were unaffected. He displayed congenital physical abnormalities including mild facial weakness, ears set at right angles to the skull, high-arched palate, valgus deformity of the elbows and inability to extend them fully, clinodactyly of the fingers and toes, syndactyly of second and third toes of both feet, thoracolumbar scoliosis and lumbar lordosis, and degenerative disease of the cervical and lumbar spine. There was clinical and electrophysiologic evidence of mild sensorimotor peripheral neuropathy, and CT scan and MRI of the brain were normal. He was reviewed neurologically at 74 years of age, at which time he had undergone surgical fusion of the lumbar spine, bilateral knee replacements, and a nephrectomy for renal carcinoma. He was able to stand and walk but used an electric wheelchair when out of doors. There was no progression of his congenital abnormalities; nerve conduction studies confirmed the presence of a mild, predominantly sensory, neuropathy. Hahn et al. (2010) reported 2 Hungarian sisters, born of nonconsanguineous parents, who presented in their early twenties with disabling sweating of the upper body in response to cold temperatures or nervousness. Onset of symptoms occurred around age 10 years. Both patients had difficulty sweating during hot weather and often became overheated in such situations. However, heat-induced mild sweating localized primarily to the lumbar region, groin, and legs. Detailed histories revealed that both had severe feeding difficulties in infancy due to poor sucking and swallowing and required nasogastric feeding or gastrostomy tube. When crying or touched, they assumed an opisthotonus-like posture and developed facial muscle contractions with trismus and hypersalivation. Apnea occurred during some of these episodes. One sister had episodes of unexplained fevers, but records for the younger sister were not as detailed. These features abated during the first 2 years of life, and both showed normal psychomotor development, although there was some residual facial muscle weakness. There were mild dysmorphic features apparent from birth, including round face, depressed nasal bridge, anteverted nostrils, long philtrum, high-arched palate, micrognathia, camptodactyly, contractures of the elbows, and dry, scaly skin. Both patients developed scoliosis later in childhood. Neurologic examination as adults showed decreased pain and temperature sensation in the fingers; there were no signs of autonomic dysfunction. The cold-induced sweating abnormalities were alleviated by treatment with clonidine, a central alpha-2-adrenoreceptor agonist that blocks central sympathetic activity by inhibiting noradrenaline release via a feedback mechanism. The effect was lasting with addition of amitriptyline.
In a 74-year-old Australian man with cold-induced sweating syndrome, Rousseau et al. (2006) identified compound heterozygosity for a truncating (607672.0001) and a missense mutation (607672.0002) in the CLCF1 gene. The mutations were not found in 140 control chromosomes, ... In a 74-year-old Australian man with cold-induced sweating syndrome, Rousseau et al. (2006) identified compound heterozygosity for a truncating (607672.0001) and a missense mutation (607672.0002) in the CLCF1 gene. The mutations were not found in 140 control chromosomes, and no disease-related mutations were identified in several other genes involved in the ciliary neurotrophic factor (CNTF; 118945) pathway. In 2 Hungarian sisters with CISS2, Hahn et al. (2010) identified compound heterozygous mutations in the CLCF1 gene (607672.0003 and 607672.0004).