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Multiple benign circumferential skin creases on limbs

General Information (adopted from Orphanet):

Synonyms, Signs:	MTBS CCSF Kunze-Riehm syndrome michelin tire baby syndrome Congenital circumferential skin folds
Number of Symptoms	38
OrphanetNr:	2505
OMIM Id:	156610
ICD-10:	Q82.8
UMLs:	C0473586
MeSH:	C537575
MedDRA:
Snomed:	239142006

Prevalence, inheritance and age of onset:

Prevalence:	No data available.
Inheritance:	Autosomal dominant inheritance [Omim]
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases:

Unclassified genetic skin disease
-Rare genetic disease
-Rare skin disease

Symptom Information: Sort by abundance

	Symptom Information	Symptom	Abundance	DB Freq
1	(HPO:0000045)	Abnormality of the scrotum	Occasional [Orphanet]	14 / 7739
2	(HPO:0000047)	Hypospadias	Occasional [Orphanet]	250 / 7739
3	(HPO:0000035)	Abnormality of the testis	Occasional [Orphanet]	296 / 7739
4	(HPO:0000175)	Cleft palate		349 / 7739
5	(HPO:0000252)	Microcephaly	Occasional [Orphanet]	832 / 7739
6	(HPO:0000277)	Abnormality of the mandible	Occasional [Orphanet]	394 / 7739
7	(HPO:0000343)	Long philtrum	Occasional [Orphanet]	262 / 7739
8	(HPO:0000606)	Abnormality of the periorbital region	Occasional [Orphanet]	96 / 7739
9	(HPO:0000286)	Epicanthus	Occasional [Orphanet]	371 / 7739
10	(HPO:0000174)	Abnormality of the palate	Frequent [Orphanet]	298 / 7739
11	(HPO:0000271)	Abnormality of the face	Occasional [Orphanet]	108 / 7739
12	(HPO:0008056)	Aplasia/Hypoplasia affecting the eye	Occasional [Orphanet]	142 / 7739
13	(HPO:0000488)	Retinopathy	Occasional [Orphanet]	75 / 7739
14	(HPO:0000482)	Microcornea	Occasional [Orphanet]	102 / 7739
15	(HPO:0000356)	Abnormality of the outer ear	Occasional [Orphanet]	85 / 7739
16	(HPO:0000357)	Abnormal location of ears	Occasional [Orphanet]	328 / 7739
17	(HPO:0006768)	Localized neuroblastoma		1 / 7739
18	(HPO:0100006)	Neoplasm of the central nervous system	Occasional [Orphanet]	34 / 7739
19	(HPO:0002817)	Abnormality of the upper limb	Occasional [Orphanet]	25 / 7739
20	(HPO:0100559)	Lower limb asymmetry	Occasional [Orphanet]	30 / 7739
21	(HPO:0004299)	Hernia of the abdominal wall	Occasional [Orphanet]	176 / 7739
22	(HPO:0001537)	Umbilical hernia	Occasional [Orphanet]	206 / 7739
23	(HPO:0004322)	Short stature	Occasional [Orphanet]	1232 / 7739
24	(HPO:0007400)	Irregular hyperpigmentation	Frequent [Orphanet]	72 / 7739
25	(HPO:0001072)	Thickened skin	Very frequent [Orphanet]	87 / 7739
26	(HPO:0000951)	Abnormality of the skin		147 / 7739
27	(HPO:0001582)	Redundant skin	Very frequent [Orphanet]	51 / 7739
28	(HPO:0011362)	Abnormal hair quantity	Occasional [Orphanet]	92 / 7739
29	(HPO:0200040)	Epidermoid cyst	Very frequent [Orphanet]	35 / 7739
30	(HPO:0001635)	Congestive heart failure	Occasional [Orphanet]	232 / 7739
31	(HPO:0030680)	Abnormality of cardiovascular system morphology		355 / 7739
32	(HPO:0000969)	Edema	Very frequent [Orphanet]	117 / 7739
33	(HPO:0003011)	Abnormality of the musculature	Occasional [Orphanet]	47 / 7739
34	(HPO:0030680)	Abnormality of cardiovascular system morphology		355 / 7739
35	(OMIM)	Circumferential deep skin folds of limbs		1 / 7739
36	(HPO:0000006)	Autosomal dominant inheritance		2518 / 7739
37	(OMIM)	Deep gyrus-like skin folds on the back		1 / 7739
38	(HPO:0012758)	Neurodevelopmental delay	Occasional [Orphanet]	949 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol	Variation	Clinical significance	Reference

Additional Information:

Clinical Description OMIM

Niikawa et al. (1985) reported 2 families with this syndrome. In the first family the trait occurred in 3 generations. The proband, a 3-year-old girl, had deep skin folds, gyrus-like on the back and circumferential in the limbs ... Niikawa et al. (1985) reported 2 families with this syndrome. In the first family the trait occurred in 3 generations. The proband, a 3-year-old girl, had deep skin folds, gyrus-like on the back and circumferential in the limbs bilaterally. Her father and maternal grandmother had several skin creases around the wrists and forearms which they claimed were remnants of deep skin folds in infancy. In the second family a 5-year-old boy and his 10-month-old brother were affected. The parents were normal; it was unknown whether they had excessive skin folds in infancy. Kunze and Riehm (1982) reported the same disorder in 2 families: in 1, a father and his son with cleft palate and localized neuroblastoma, and in the other, a father and his 2 daughters (1 with median cleft palate). The creases disappeared almost completely in later life. Multiple benign, deep, ring-shaped creases were observed in a third family, possibly as a new dominant mutation. Ross (1969) concluded that in his patient a diffuse underlying lipomatous nevus was present. Wiedemann (1987) pictured an infant with multiple benign circumferential skin creases in association with a congenital heart defect. He also called attention to the demonstration of this feature in a representation of Eve nursing her son in a detail of a bronze door at the cathedral of Hildesheim in northwestern Germany. Bass et al. (1993) described the disorder in 7 individuals in 4 generations with 3 instances of male-to-male transmission. The constricting bands were distributed symmetrically and circumferentially over the neck, forearms, and lower legs. Spontaneous resolution took place during childhood. In a karyotypically abnormal child with multiple anomalies, mental retardation, hypertrichosis, and circumferential ringed creases, Schnur et al. (1993) found an underlying smooth muscle hamartoma in a skin biopsy of 1 of the creases. The same histologic pattern was documented in 4 other children with circumferential skin creases described in 4 separate reports, e.g., Oku et al. (1993). Schnur and Zackai (1997) pointed out that the developmentally delayed, although cytogenetically normal child reported by Pivnick et al. (1996) showed ringed creases of the extremities in published photographs and had demonstrated smooth muscle hamartoma described histologically. Schnur and Zackai (1997) suggested that both karyotype and skin biopsy be performed in children with ringed skin creases, with and without other anomalies. In describing a 15-month-old girl with this syndrome, Sato et al. (1997) raised the question of a congenital disorder of elastic fiber formation in this condition. Histologic examination showed fragmented elastic fibers, in addition to smooth muscle hamartoma. On electron microscopy, decreased deposition of elastin (130160) was observed. Elliott et al. (1996) suggested that the patient reported with circumferential skin creases by Cohen et al. (1993) may have had a distinct syndrome because of an unusual pattern of associated congenital anomalies and severe psychomotor retardation. The 4-year-old male had craniofacial anomalies, cleft palate, hypoplastic scrotum, inguinal and umbilical hernias, and other abnormalities. Leonard (2002) reported a case similar to that reported by Cohen et al. (1993) and Elliott et al. (1996). The patient was a 29-month-old boy with symmetrical circumferential skin creases on the arms, legs, and digits, and other features, including epicanthal folds, microphthalmia, microcornea, microcephaly, small and low-set posteriorly angulated ears with thick overfolded helices, cleft palate, and moderate to severe psychomotor developmental delay. Kondoh et al. (2004) described a 3-year-old boy with circumferential skin creases as seen in this disorder, hearing impairment, undescended testes, short stature, and mental handicap. Skin biopsy from the inguinal region showed 'degenerative collagen.' Kondoh et al. (2004) suggested that the patient of Elliott et al. (1996) and their patient had a distinct disorder which they suggested be called HITCH syndrome for 'hearing impairment, undescended testis, circumferential skin creases, and mental handicap.' Devriendt et al. (2004) described their experience on long-term follow-up of a child presenting at birth with multiple circumferential skin creases, and suggested that these may be a sign of genetic mosaicism. The patient had mixoploidy with diploidy/triploidy mosaicism. The patient also had linear skin hyperpigmentation and limb asymmetry as well as nevus flammeus on one leg and grade IV hypospadias.

Symptoms & Signs

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