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

• Cutis Marmorata
• Rothmund-Thomson 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 addition, affected infants often have large lesions (ulcers) or complete absence of the skin in affected areas. In most cases, skin abnormalities affect the arms and legs (limbs), although the face and/or trunk may also be involved. The skin symptoms associated with CMTC often improve with age.

Some individuals affected by CMTC develop additional associated abnormalities. The estimated frequency ranges from 20 to 80 percent of cases. Additional abnormalities include the development of pink or dark red, irregularly shaped patches of skin ("port wine stain" or nevus flammeus), elevated pressure within the eye (glaucoma), over- or undergrowth (hyper- or hypotrophy) of an affected limb, and abnormal thinness of an affected limb.

Less common associated symptoms may include an underdeveloped jaw (micrognathia); webbing of the toes (syndactyly); wasting of one side of the body (hemiatrophy); malformation of a limb; unbalanced body development; and neurological abnormalities including psychomotor retardation.

A few individuals may have other symptoms such as a detached retina of the eye, high blood pressure (hypertension), abnormal placement of the urinary opening (meatus) on the underside of the penis (hypospadias), and/or growth deficiencies.

Macrocephaly-cutis marmorata telangiectatica congenita (M-CMTC) is a rare, distinct phenotype of CMTC in which the characteristic skin abnormalities of CMTC occur in infants who are abnormally large at birth (somatic overgrowth or macrosomia) and have an abnormally large head (macrocephaly) and/or brain (megalencephaly). Infants with M-CMTC are at a risk of developing associated neurological abnormalities including developmental delays, mental retardation, and the accumulation of excessive cerebrospinal fluid in the (hydrocephalus). Although infants are large at birth, they may experience growth deficiencies after birth (postnatal growth deficiency).

Infants with M-CMTC may exhibit additional symptoms including a prominent forehead (frontal bossing), webbing of the toes and fingers (syndactyly), decreased muscle tone (hypotonia), loose (hyperelastic) skin, and loose joints (joint laxity). Affected infants may also experience unequal development of the face and legs (facial and limb asymmetry) and abnormal development of a sac within a vein due to widening or "ballooning" (dilation) of the walls of the affected vein (venous aneurysm). In rare cases, congenital heart defects or seizures may occur.

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 also occur in conjunction with other syndromes.

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.)

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.)

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 (hypoplastic) fingers and toes 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). 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 and M-CMTC often go away without treatment (spontaneous remission) within the first two years of life. Other treatment is symptomatic and supportive.

Infants with CMTC and M-CMTC should receive a thorough clinical evaluation because of the potential development of associated abnormalities (e.g., glaucoma, syndactyly, neurological abnormalities, eye abnormalities, asymmetry of the limbs or face). Treatment may require the coordinated efforts of a team of specialists. Pediatricians, orthopedic surgeons, specialists who assess and treat eye problems (ophthalmologists), neurologists, and other health care professionals may need to systematically and comprehensively plan an affected child's treatment.

When other family members are affected genetic counseling may be of benefit.
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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 website.

For information about clinical trials being conducted at the National Institutes of Health (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

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.