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MedGen UID:
Concept ID:
Disease or Syndrome
Synonyms: Cold-induced sweating syndrome 3; PERCHING
Gene (location): KLHL7 (7p15.3)
Monarch Initiative: MONDO:0014890
OMIM®: 617055
Orphanet: ORPHA603684


PERCHING syndrome is an autosomal recessive multisystem disorder characterized by global developmental delay, dysmorphic facial features, feeding and respiratory difficulties with poor overall growth, axial hypotonia, and joint contractures. The features are variable, even within families, and may also include retinitis pigmentosa, cardiac or genitourinary anomalies, and abnormal sweating. Each letter of the PERCHING acronym represents 2 important phenotypic elements: Postural and Palatal abnormalities; Exophthalmos and Enteral-tube dependency/feeding issues; Respiratory distress and Retinitis pigmentosa; Contractures and Camptodactyly; Hypertelorism and Hirsutism; Intrauterine growth retardation (IUGR)/growth failure and Intellectual disability/developmental delay; Nevus flammeus and Neurologic malformations; and facial Gestalt/grimacing and Genitourinary abnormalities (Jeffries et al., 2019). Death in infancy or early childhood often occurs, although survival to the third decade has been reported. Some of the features, such as contractures, dysmorphic craniofacial features, and severe feeding difficulties, are reminiscent of Bohring-Opitz syndrome (605039) (summary by Kanthi et al., 2019 and Buers et al., 2020). [from OMIM]

Additional description

From MedlinePlus Genetics
Many of the health problems associated with Crisponi syndrome improve with time, and affected individuals who survive the newborn period go on to develop other features of cold-induced sweating syndrome in early childhood. Within the first decade of life, affected individuals begin having episodes of profuse sweating (hyperhidrosis) and shivering involving the face, torso, and arms. The excessive sweating is usually triggered by exposure to temperatures below about 65 or 70 degrees Fahrenheit, but it can also be triggered by nervousness or eating sugary foods. Paradoxically, affected individuals tend not to sweat in warmer conditions, instead becoming flushed and overheated in hot environments.

Adolescents with cold-induced sweating syndrome typically develop abnormal side-to-side and front-to-back curvature of the spine (scoliosis and kyphosis, often called kyphoscoliosis when they occur together). Although infants may develop life-threatening fevers, affected individuals who survive infancy have a normal life expectancy.

Infants with Crisponi syndrome have unusual facial features, including a flat nasal bridge, upturned nostrils, a long space between the nose and upper lip (philtrum), a high arched roof of the mouth (palate), a small chin (micrognathia), and low-set ears. The muscles in the lower part of the face are weak, leading to severe feeding difficulties, excessive drooling, and breathing problems. Other physical abnormalities associated with Crisponi syndrome include a scaly skin rash, an inability to fully extend the elbows, overlapping fingers and tightly fisted hands, and malformations of the feet and toes. Affected infants startle easily and often tense their facial muscles into a grimace-like expression. By six months of age, infants with Crisponi syndrome develop unexplained high fevers that increase the risk of seizures and sudden death.

Cold-induced sweating syndrome is characterized by problems with regulating body temperature and other abnormalities affecting many parts of the body. In infancy, the features of this condition are often known as Crisponi syndrome. Researchers originally thought that cold-induced sweating syndrome and Crisponi syndrome were separate disorders, but it is now widely believed that they represent the same condition at different times during life.  https://medlineplus.gov/genetics/condition/cold-induced-sweating-syndrome

Clinical features

From HPO
MedGen UID:
Concept ID:
Disease or Syndrome
Difficulty in swallowing.
Feeding difficulties
MedGen UID:
Concept ID:
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Flexion contracture
MedGen UID:
Concept ID:
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
MedGen UID:
Concept ID:
Congenital Abnormality
The distal interphalangeal joint and/or the proximal interphalangeal joint of the fingers or toes cannot be extended to 180 degrees by either active or passive extension.
Respiratory distress
MedGen UID:
Concept ID:
Sign or Symptom
Respiratory distress is objectively observable as the physical or emotional consequences from the experience of dyspnea. The physical presentation of respiratory distress is generally referred to as labored breathing, while the sensation of respiratory distress is called shortness of breath or dyspnea.
MedGen UID:
Concept ID:
Sign or Symptom
Body temperature elevated above the normal range.
High palate
MedGen UID:
Concept ID:
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Depressed nasal bridge
MedGen UID:
Concept ID:
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Full cheeks
MedGen UID:
Concept ID:
Increased prominence or roundness of soft tissues between zygomata and mandible.
Rod-cone dystrophy
MedGen UID:
Concept ID:
Disease or Syndrome
An inherited retinal disease subtype in which the rod photoreceptors appear to be more severely affected than the cone photoreceptors. Typical presentation is with nyctalopia (due to rod dysfunction) followed by loss of mid-peripheral field of vision, which gradually extends and leaves many patients with a small central island of vision due to the preservation of macular cones.

Professional guidelines


Horton-Bell M, Hamilton S, Keelagher R, Allen S, De Burca A, Ioannou C, Impey L, Cilliers D
Prenat Diagn 2022 Nov;42(12):1481-1483. Epub 2022 Oct 21 doi: 10.1002/pd.6249. PMID: 36217303

Recent clinical studies


Horton-Bell M, Hamilton S, Keelagher R, Allen S, De Burca A, Ioannou C, Impey L, Cilliers D
Prenat Diagn 2022 Nov;42(12):1481-1483. Epub 2022 Oct 21 doi: 10.1002/pd.6249. PMID: 36217303
Makay P, Mubungu G, Mupuala A, Bluske K, Brown C, Schmidt SA, Ngole M, Fuanani P, Perry DL, Lukusa P, Devriendt K, Taft RJ, Lumaka A
Am J Med Genet A 2022 Sep;188(9):2825-2831. Epub 2022 Jun 7 doi: 10.1002/ajmg.a.62855. PMID: 35670385

Clinical prediction guides

Yilmaz Gulec E, Turgut GT, Gezdirici A, Karaman V, Ozturk FN, Avci S, Kalayci T, Senturk L, Ayaz A, Kayserili H, Uyguner ZO, Altunoğlu U
Clin Genet 2022 Sep;102(3):201-217. Epub 2022 Jul 12 doi: 10.1111/cge.14177. PMID: 35699517

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