Cold-Induced Sweating Syndrome Including Crisponi Syndrome

CLINICAL CHARACTERISTICS

Cold-induced sweating syndrome (CISS) and its infantile presentation, Crisponi syndrome(CS) is characterized by dysmorphic features (distinctive facies, lower facial weakness, flexion deformity at the elbows, camptodactyly with fisted hands, misshapen feet, and overriding toes); intermittent contracture of facial and oropharyngeal muscles when crying or being handled with puckering of lips and drooling of foamy saliva often associated with laryngospasm and respiratory distress; excessive startling and opisthotonus-like posturing with unexpected tactile or auditory stimuli; poor suck reflex and severely impaired swallowing; and a scaly erythematous rash. During the first decade of life, children with CISS/CS develop profuse sweating of the face, arms, and chest with ambient temperatures below 18º to 22º C, and with other stimuli including nervousness or ingestion of sweets. Affected individuals sweat very little in hot environments and may feel overheated. Progressive thoracolumbar kyphoscoliosis occurs, requiring intervention in the second decade.

DIAGNOSIS/TESTING: The diagnosis of CISS/CS is established in a proband with suggestive findings and biallelic pathogenic variants in either or identified on molecular genetic testing

MANAGEMENT

Supplemental oxygen is needed for laryngospasm with respiratory distress and cooling blankets for bouts of hyperthermia; intervention for feeding difficulties is necessary over the first year of life; bracing and physical therapy for camptodactyly and prolonged bracing or surgical intervention may be required to treat a progressive thoracolumbar scoliosis. Topical lubrication needed to avoid corneal alterations and regular dental care needed to avoid excessive dental decay. Options for the treatment of cold-induced sweating include clonidine alone, clonidine plus amitryptyline, or moxonidine alone. Evaluate for scoliosis. Ophthalmologic evaluation for corneal injury every six months and yearly dental visits due to early dental decay are recommended. Heat exposure and prolonged physical activity in a hot climate. : Pharmacologic treatments for cold-induced sweating should be discontinued during pregnancy, as teratogenic effects on the fetus have not been well studied and remain a possibility. The prescription of clonidine should not be discontinued abruptly; the drug should be phased out over four to six days.

GENETIC COUNSELING

CISS/CS is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a or pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the or pathogenic variants have been identified in an affected family member, carrier testing for at-risk family members, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible.