Table 3.

Genes and Disorders of Interest in the Differential Diagnosis of Cold-Induced Sweating Syndrome / Crisponi Syndrome (CISS/CS)

GeneDisorderMOIClinical Characteristics & Overlapping FeaturesDistinguishing Features
KLHL7 PERCHING syndrome (OMIM 617055)ARInfants w/PERCHING syndrome may resemble those w/CISS/CS: both disorders are assoc w/paroxysmal oropharyngeal muscle contractions, swallowing & feeding difficulties, typical dysmorphic features, & camptodactyly. 1 Some persons w/PERCHING syndrome have hyperthermia & signs of retinitis pigmentosa.Unlike CISS/CS, few persons w/PERCHING syndrome survive childhood, & none has demonstrated cold-induced sweating.
LIFR 2Stüve-Wiedemann syndrome (STWS) (OMIM 601559)ARDysmorphic facial features; camptodactyly; severe sucking, swallowing, & feeding difficulties; stimulus-induced abnormal posturing & episodic facial contractions; laryngospasm causing respiratory distress; episodes of hyperthermia & sudden death. 2 Persistent heat intolerance & paradoxic cold-induced sweating. 3 Teens may manifest ↓ pain perception, signs of corneal injuries & scarring, early dental decay, & progressive kyphoscoliosis.Chondrodysplasia (manifest as congenital bowing of the long bones & ↓ joint mobility) is the main differentiating characteristic. (Note: STWS w/cold-induced sweating but w/o bowing of long bones has been reported. 4)
MAGEL2 Schaaf-Yang syndrome (SYS)AD 5Neurodevelopmental disorder similar to Prader-Willi syndrome. Manifest at birth w/generalized hypotonia, sucking & feeding difficulties, episodic severe respiratory distress & sleep apnea, & distal joint contractures. Children show marked DD & speech delay, & exhibit autistic behavior & ID.Infants w/SYS do not present w/characteristic dysmorphic features, episodic facial contractions, or stimulus-induced posturing typical of CISS/CS. SYS is not assoc w/hyperthermia or impaired thermoregulation.
MYH3 Distal arthrogryposis types 2A & 2B (DA2A/DA2B) (OMIM 193700 & 601680)ADSevere distal arthrogryposis & joint contractures; "whistling face" (intermittent facial muscle contraction & puckering of lips) that may resemble facial movements in young children w/CISS/CSIn infants w/CISS/CS (but not in DA2A/DA2B), puckering of lips is provoked by crying. In DA2A/DA2B, puckering of lips may occur when resting or sleeping. Microstomia (seen in DA2A/DA2B) is not assoc w/CISS/CS.
NALCN Congenital contractures of the limbs & face, hypotonia, & DD (CLIFAHDD) (OMIM 616266)ADStriking similarity w/CISS/CS: facial dysmorphisms, distal arthrogryposis & camptodactyly; micrognathia, impaired sucking, swallowing, & feeding w/need for long-term NG tube feeding; episodic stimulus-induced facial & oropharyngeal contractions, pursing of lips & excessive salivation, inspiratory stridor, & hypoxemia. Spells occur only during waking & incl excessive sweating in face, head, & upper trunk. 7Unlike CISS/CS, CLIFAHDD is assoc w/persistent severe axial hypotonia, precarious respiratory status, & DD.

AD = autosomal dominant; AR = autosomal recessive; CISS = cold-induced sweating syndrome; CS = Crisponi syndrome; DD = developmental delay; ID = intellectual disability; MOI = mode of inheritance; NG = nasogastric

1.
2.
3.
4.

Melone et al [2014] reported a female age 33 years with features of STWS including cold-induced sweating, but without bowing of the long bones and complete chromosome 5 maternal isodisomy with an isozygous LIFR pathogenic variant (c.2170C>G, p.Pro724Ala). The proband’s mother was heterozygous for the c.2170C>G variant.

5.

Schaaf-Yang syndrome is inherited in an autosomal dominant, maternally imprinted manner (i.e., a heterozygous pathogenic variant on the paternally derived MAGEL2 allele results in disease; a pathogenic variant on the maternally derived MAGEL2 allele does not result in disease because normally the maternally derived MAGEL2 allele is silenced).

6.
7.

From: Cold-Induced Sweating Syndrome Including Crisponi Syndrome

Cover of GeneReviews®
GeneReviews® [Internet].
Adam MP, Feldman J, Mirzaa GM, et al., editors.
Seattle (WA): University of Washington, Seattle; 1993-2024.
Copyright © 1993-2024, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2024 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.