Information on the following diseases can be found in the Related Disorders section of this report:

• Cutis Marmorata
• Klippel-Trenaunay syndrome
• Sturge-Weber syndrome
• Adams-Oliver syndrome

In most cases, the symptoms of CMTC are present at birth (congenital). Affected infants are characterized by discolored patches of skin caused by widened (dilated) surface blood vessels (livedo reticularis telangiectases). The affected areas of skin have a "marbled" or "fishnet" appearance (cutis marmorata). In most cases, skin abnormalities affect the arms and legs (limbs), although the trunk may also be involved. Facial involvement is rare. The skin symptoms associated with classical CMTC improve with age and usually disappear completely around puberty. Atrophic patches may remain. The soft tissue hypoplasia can likewise remain present, in particular if muscles are affected. This has no consequences for normal functionality.

A plethora of associated abnormalities have been reported. However, careful evaluation of these and more recent cases strongly suggests that the skin abnormalities in these patients are not CMTC but capillary malformations. These can be associated with several syndromic disorders. The ones most commonly mistaken for CMTC variants are Klippel-Trenaunay syndrome, Cowden's disease and M-CMTC. Rarely, Adams-Oliver and Proteus(-like) syndrome underlie the vascular abnormalities.

The exact cause of CMTC is not known. Most cases occur randomly, for no apparent reason (spontaneously). Researchers believe that several factors (e.g., a virus) may contribute to the development of the disorder (multifactorial). In a few rare cases, it has appeared that CMTC may occasionally run in families (familial cases).

CMTC affects males and females in equal numbers and is present at birth (congenital). Fewer than 300 cases of CMTC have been reported in the medical literature. Since many cases of CMTC are mild and clear up without treatment, the disorder may be under-diagnosed making it difficult to determine the true frequency of CMTC in the general population. More than 70 cases of M-CMTC have been reported in the medical literature.

Symptoms of the following disorders can be similar to those of CMTC. Comparisons may be useful for a differential diagnosis:

Cutis marmorata is a transient skin disorder in which the skin has a bluish red marbling pattern when exposed to cold temperatures. This condition is found most often in infants but may also affect adults. When the skin is warmed the condition disappears. Cutis marmorata is very common in premature infants and usually disappears completely at two months of age. Cutis marmorata may occur in conjunction with other syndromes but is not diagnostic.

Klippel-Trenaunay syndrome, a rare disorder that is present at birth (congenital), is characterized by abnormal benign growths on the skin (cutaneous) consisting of masses of blood vessels (hemangiomas), excessive growth (hypertrophy) of the soft tissue and bone of a leg and/or arm (limb), and varicose veins. In individuals with the disorder, such hypertrophy typically affects one side of the body (hemihypertrophy). In many cases, hemangiomas may consist of distinctive purplish-reddish birthmarks ("port wine stain" or nevus flammeus) on certain areas of the skin. The symptoms and findings associated with the disorder may vary in range and severity from case to case. (For more information on this disorder, choose "Klippel-Trenaunay" as your search term in the Rare Disease Database.)

Sturge-Weber syndrome is a rare inherited disorder characterized by the presence of a port wine colored birthmark (angioma) on the facial area and intracranial abnormalities that are present at birth (congenital). Affected infants may also have an enlarged head (macrocephaly). Generalized seizures and additional neurological symptoms usually occur between one and two years of age. Vascular lesions (telangiectasias and angiomas) in the brain usually involve the occipital or parieto-occipital regions. Glaucoma may be present in the eye located on the same side of the face where the port wine stain occurs. This eye may also be enlarged. The iris may remain blue, even though the other eye may change to another color as the infant matures. Sight in half of the visual field may be defective or absent in the affected eye. (For more information on this disorder, choose "Sturge Weber" as your search term in the Rare Disease Database.)

SWS and KTS are probably manifestations of the same underlying genetic defect.


Adams-Oliver syndrome (AOS) is an extremely rare inherited disorder characterized by defects of the scalp and abnormalities of the fingers, toes, arms, and/or legs. The physical abnormalities associated with this disorder vary greatly among affected individuals. Some cases may be very mild while others may be severe. In infants with Adams-Oliver syndrome, scalp defects are present at birth (congenital) and may include one or multiple hairless scarred areas that may have abnormally wide (dilated) blood vessels directly under the affected skin. In severe cases, an underlying defect of the bones of the skull may also be present. In addition, infants with this disorder typically have malformations of the hands, arms, feet, and/or legs. These range from abnormally short fingers and toes with small or absent nails to absent hands and/or lower legs. In some cases, additional abnormalities may also be present. Some cases of Adams-Oliver syndrome occur randomly as the result of a spontaneous genetic change (i.e., new mutation). An association with CMTC has been reported but may have been a coincidence. Inheritance is autosomal dominant. (For more information on this disorder, choose "Adams-Oliver" as your search term in the Rare Disease Database.)

Diagnosis
The diagnosis of CMTC may be confirmed by a thorough clinical evaluation, a detailed patient history, and identification of characteristic findings.

Treatment
The skin abnormalities associated with CMTC often go away without treatment (spontaneous remission) within the first years of life. Other treatment is symptomatic and supportive. CMTC of the legs can be associated with early development of superficial venous insufficiency which may require treatment.

Infants with a diagnosis of CMTC and associated abnormalities should be referred to a specialist centre and, if indicated, receive a thorough clinical evaluation to reach a definitive diagnosis. No diagnostic procedures are required if the diagnosis is typical isolated CMTC.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:219250; Last Update:3/13/01. Entry No:602501; Last Update:8/23/01.

TEXTBOOKS
Gerritsen MJP, Gerritsen R. Cutis Marmorata Telangiectatica Congenita. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:1000.

Buyce ML, ed. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific Publications; For: The Center for Birth Defects Information Services Inc; 1990: 476-77.

REVIEW ARTICLES
Robertson SP, et al. Macrocephaly-cutis marmorata telangiectatica congenita: report of five cases and review of the literature. Clin Dysmorphol. 2000;9:1-9.

Pehr K, Moroz B. Cutis marmorata telangeictatica congenita: long-term follow-up, review of the literature, and report of a case in conjunction with congenital hypothyroidism. Pediatr Dermatol. 1993;10:6-11.

Picascia DD. Esterly NB, Cutis marmorata telangeictatica congenita: a report of 22 cases. J Am Acad Dermatol. 1989;20:1098-1104.

JOURNAL ARTICLES
Lapunzina P, et al. Macrocephaly-cutis marmorata telangiectasia congenita: report of six new patients and a review. Am J Med Genet. 2004;15:45-51.

Akcar N, et al. A case of macrocephaly-cutis marmorata telangiectasia congenita and review of neuroradiologic features. Ann Genet. 2004;47:261-5.

Giuliano F, et al. Macrocephaly-cutis marmorata telangiectasia congenita: seven cases including two with unusual cerebral manifestations. Am J Med Genet. 2004;126A:99-103.

Garzon MC, Schweiger E. Cutis marmorata telangiectasia congenita. Semin Cutan Med Surg. 2004;23:99-106.

Yano S, Watanabe Y. Association of arrhythmia and sudden death in macrocephaly-cutis marmorata telangiectatica congenita syndrome. Am J Med Genet. 2001;102:149-52.

Ben-Amitai D, et al. Cutis marmorata telangeictatica congenita and hypospadias: report of 4 cases. J Am Acad Dermatol. 2001;45:131-32.

Amitai DB, et al. Cutis marmorata telangeictatica congenita: clinical findings in 85 patients. Pediatr Dermatol. 2000;17:100-04.

Franceschini P, et al. Macrocephaly-cutis marmorata telangiectatica congenita without cutis marmorata? Am J Med Genet. 2000;90:265-69.

Gerritsen MJ, et al. Cutis marmorata telangiectatica congenita: a report of 18 cases. Br J Dermatol. 2000;142:366-69.

Devillers AC, et al. Cutis marmorata telangeictatica congenita: clinical features in 35 cases. Arch Dermatol. 1999;135:34-38.

Vogels A, et al. The macrocephaly-cutis marmorata telangiectatica congenita syndrome. Long-term follow-up data in 4 children and adolescents. Genet Couns. 1998;9:245-53.

Carcao M, et al. MRI findings in macrocephaly-cutis marmorata telangiectatica congenita. Am J Med Genet. 1998;76:165-67.

Clayton-Smith J, et al. Macrocephaly with cutis haemangioma and syndactyly-a distinctive overgrowth syndrome. Clin Dysmorphol. 1997;6:291-302.

Moore CA, et al. Macrocephaly-cutis marmorata telangiectatica congenita: a distinct disorder with developmental delay and connective tissue abnormalities. Am J Med Genet. 1997;70:67-73.

Pendergast SD, et al. Ocular findings in cutis marmorata telangeictatica congenita. Bilateral exudative vitreoretinopathy. Retina. 1997;17:306-09.

Mayser P, et al. Cutis marmorata telangeictatica congenita (Van Lohuizen syndrome). Hautarzt. 1992;43:721-23.

Toriello HV, Graff RG, Florentine MF, Lacina S, Moore WD. Scalp and limb defects with cutis marmorata telangiectatica congenita: Adams-Oliver syndrome? Am J Med Genet. 1988;29:269-76.

Toriello HV, Mulliken JB. Accurately renaming macrocephaly-cutis marmorata telangiectatica congenita (M-CMTC) as macrocephaly-capillary malformation (M-CM).Am J Med Genet A 2007;143A:3009