Crisponi syndrome is a rare disorder characterized by congenital spasms of orofacial muscles, with trismus in response to tactile stimuli and during crying. Characteristic dysmorphic features include round face, chubby cheeks, micrognathia, camptodactyly, and progressive kyphoscoliosis. Major feeding and respiratory difficulties with hyperthermia occur in the course of the disease and usually lead to death in the first months of life. Later on, hyperexcitability disappears in the rare survivors, but children develop impaired thermoregulation and disabling abnormal sweating in response to cold temperatures, and sweat very little with heat.

The differential diagnosis of Crisponi syndrome includes Stüve-Wiedemann syndrome with a significant symptomatic overlap between the two. However, the main features of Stüve-Wiedemann syndrome; congenital bowing of the lower limbs with internal cortical thickening and metaphyseal changes have not been reported in patients with Crisponi syndrome. Medical intervention is needed in the neonatal period due to impaired sucking and swallowing that result in poor feeding. For those who survive infancy with this disorder, Clonidine can be used to treat abnormal sweating.

Homozygous or compound heterozygous cytokine receptor-like factor 1 (CRLF1) mutations were identified in Crisponi syndrome patients. Sweating is normally controlled by the sympathetic nervous system, and the neurons that innervate sweat glands differentiate in a neurokine-dependent manner. In this context, CRLF1 complexes with cardiotrophin-like cytokine factor 1 (CLCF1) to induce cholinergic differentiation of sympathetic neurons in culture. Therefore loss-of-function mutations in CRLF1 are thought to result in perturbation of the cytokine complex function, causing a defect in cholinergic differentiation in sweat glands during development.