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

• Cutis marmorata
• Cutis marmorata telangiectatica congenita syndrome
• Klippel-Trenaunay syndrome
• Sturge-Weber syndrome

Infants born with macrocephaly, cutis marmorata telangiectatica congenita (M-CMTC) are abnormally large at birth (somatic overgrowth or macrosomia) and have an abnormally large head (macrocephaly) and/or brain (megalencephaly). Such babies show a marbled or reticulated pattern of veins on their skin surface that does not resolve with warming of the skin. These lesions are believed to be a form of a vascular malformation composed of small-sized vessels within the skin. In addition to the marbled vascular malformation, affected individuals may also have a vascular patch (made up of the merging of separate capillary malformations, port wine stain nevus flammeus ) located on the central part of the face. Infants with M-CMTC are at greater risk of developing associated neurological abnormalities, including developmental delays, mental retardation, and the accumulation of excessive cerebrospinal fluid in the skull (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 M-CMTC is not known. Most cases occur randomly, for no apparent reason (spontaneously). Some researchers believe that several factors (among them, a virus) may contribute to the development of the disorder (multi-factorial).

Only about 75 cases of M-CMTC have been reported in the world’s medical literature. One review of cases suggests that slightly more males than females (41:33) are affected.

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.

Cutis marmorata telangiectatica congenita syndrome (CMTC) is a rare type of vascular malformation composed predominantly of capillary and vein-sized vessels within the skin. The skin lesions are characterized by a lace-like vascular pattern, often pink-purple in color, that may involve a limited or more widespread area of the skin surface. As a result, the skin has a purple or blue marbled or "fishnet" appearance resembling cutis marmorata. In some affected individuals, thinning of the skin (atrophy), breakdown (ulceration) or complete absence of the skin in affected areas may also be present. From 27 to 50% (see references) of affected individuals have additional associated abnormalities including pink or dark red, irregularly shaped patches of skin (capillary malformation, port wine stain, nevus flammeus); loss of muscle tissue (wasting) on one side of the body (hemiatrophy); elevated fluid pressure within the eye (glaucoma); and/or reduced growth of one leg. (For more information on this disorder, choose "cutis marmorata telangiectasia congenita syndrome" as your search term in the Rare Disease Database.)

Klippel-Trenaunay syndrome, a rare disorder that is present at birth (congenital), is characterized by the presence of a capillary vascular malformation (port wine stain) on the skin of an arm or leg (cutaneous) occurring in association with) excessive growth (hypertrophy) of the soft tissue and bone of that leg and/or arm (limb), and varicose veins (venous malformations). Some affected individuals will also have an underlying lymphatic malformation of the affected limb. In individuals with the disorder, such hypertrophy typically affects one limb or one side of the body (hemihypertrophy). 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 capillary vascular malformation (port wine stain) typically affecting the upper face and area around the eyes occurring in association with vascular malformations of the lining of the brain (leptomeninges) and eye that leads to glaucoma. Affected infants may also have an enlarged head (macrocephaly). Generalized seizures and additional neurological symptoms usually occur between one and two years of age. The vascular malformations (telangiectatica) 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.)

Diagnosis
The diagnosis of M-CMTC may be confirmed by a thorough clinical evaluation, a detailed patient history, and identification of characteristic findings. Recent investigations suggest that antenatal diagnosis is reliable. For a comprehensive summary of signs, symptoms and diagnosis, see The Condition in the From the Internet section of the references below.

Treatment
The skin abnormalities associated with M-CMTC may go away without treatment (spontaneous remission) within the first two years of life. Other treatment is symptomatic and supportive.

Infants with M-CMTC, like those with CMTC, should receive a thorough clinical evaluation because of the potential development of associated abnormalities (e.g., 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 healthcare 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.

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). The Johns Hopkins University. Megalencephaly-Cutis Marmorata Telangiectatica Congenital. Entry Number; 602501: Last Edit Date; 12/2/2004.

TEXTBOOKS
Champion RH, Burton JL, Ebling FJG. eds. Textbook of Dermatology. 5th ed. Blackwell Scientific Publications. London, UK; 1992.

Habif TP. Ed. Clinical Dermatology. 2nd ed. The C.V. Mosby Company. St. Louis, MO; 1990.

REVIEW ARTICLES
Lapunzina P, Gairi A, Delicado A, et al. Macrocephaly-cutis marmorata telangiectatica congenita: report of six new patients and a review. Am J Med Genet A. 2004;130:45-51.

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

Magarbane A, Haddad J, Lyonnet S, et al. Child with overgrowth, pigmentary streaks, polydactyly, and intestinal lymphangiectasia: macrocephaly-cutis marmorata telangiectatica congenita syndrome or new disorder. Am J Med Genet A. 2003;116:184-87.

Robertson SP, Gattas M, Rogers M, et al. Macrocephaly-cutis marmorata telangiectatica congenita: report of five patients and a review of the literature. Clin Dysmorphol. 2000;9:1-9.

JOURNAL ARTCILES
Nyberg RH, Uotila J, Kirkinen P, et al. Prenat Diagn. 2005;25:129-32.

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

Stoll C. Macrocephaly-cutis marmorata telangiectatica congenital: report of a patient with a translocation. Genet Couns. 2003;14:173-79.

Schwartz IV, Felix TM, Riegel M, et al. Atypical macrocephaly-cutis marmorata telangiectatica congenital with retinoblastoma. Clin Dysmorphol. 2002;11:199-202.

FROM THE INTERNET
Clayton-Smith J. M-CMTC Syndrome. Contact A Family. Last updated February 2002. 3pp.
www.cafamily.org.uk/Direct/m10.html

Syed SB. Vascular Birthmarks. Contact A Family. Last updated August 2001. 4pp.
www.cafamily.org.uk/Direct/v13.html

The Condition. Macrocephaly-CMTC. Updated June 2005. 1p.
www.macrocephaly-cmtc/thecondition.htm