De Santis Cacchione Syndrome

National Organization for Rare Disorders, Inc.

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It is possible that the main title of the report De Santis Cacchione Syndrome is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.


  • Xerodermic Idiocy

Disorder Subdivisions

  • None

General Discussion

De Sanctis-Cacchione syndrome is an extremely rare disorder characterized by the skin and eye symptoms of xeroderma pigmentosum (XP) occurring in association with neurological abnormalities, mental retardation, unusually short stature (dwarfism), and underdevelopment of the testes or ovaries (hypogonadism). Xeroderma pigmentosum is a group of rare inherited skin disorders characterized by a heightened reaction to ultraviolet light (photosensitivity), skin discolorations, and the possible development of several types of eye disorders and skin cancers. The most common neurological abnormalities associated with De Sanctis- Cacchione syndrome are low intelligence, an abnormally small head (microcephaly), the loss of ability to coordinate voluntary movement (ataxia), and/or absent (areflexia) or weakened (hyporeflexia) reflexes. De Sanctis-Cacchione syndrome is inherited as an autosomal recessive trait.


In De Sanctis-Cacchione syndrome, the earliest symptoms are the skin abnormalities associated with xeroderma pigmentosum (XP) including excessive freckling and blistering occurring after exposure to ultraviolet light (photosensitivity). In some cases, pain and blistering may occur immediately after contact with sunlight. Acute sunburn and persistent redness or inflammation of the skin (erythema) are also early symptoms of De Sanctis-Cacchione syndrome. In most cases of XP, these symptoms may be apparent immediately after birth or by the age of three years. However, in some rare cases, symptoms may not be apparent until later in childhood. In most cases of De Sanctis-Cacchione syndrome, onset is often during infancy.

Additional skin symptoms often associated with De Sanctis-Cacchione syndrome include unusually dark (hyperpigmentation) or light (hypopigmentation) areas of skin. In some cases, complete loss of skin color (depigmentation) and/or excessive scarring may occur. Wart-like lesions (actinic keratoses) may develop, as well as small red skin lesions (telangiectasias) that are caused by abnormal widening of tiny blood vessels near the surface of the skin. The skin may also become weak and easily damaged. Degenerative (atrophic) changes may occur and the skin may appear dry and smooth.

Most children with De Sanctis-Cacchione syndrome usually have one or more neurological abnormalities; the most frequent is low intelligence. Other abnormalities may include an unusually small head (microcephaly); hearing impairment (sensorineural deafness); absent (areflexia) or weakened (hyporeflexia) reflexes; and/or increased rigidity in some muscles causing stiffness and limitation of movement (spasticity). Affected individuals may also exhibit loss of the ability to coordinate voluntary movements (ataxia) and/or abnormal involuntary movements of the body such as uncontrolled jerky movements combined with slow, writhing movements (choreoathetosis).

De Sanctis-Cacchione syndrome is occasionally associated with slow progressive degeneration of part of the brain known as the cerebellum (cerebellar atropy) and/or any of a group of progressive disorders involving degeneration of other parts of the brain (i.e., cortex, basis pontis, and inferior olivary nuclei). This clinical picture is similar to that seen in the hereditary olivopontocerebellar atrophies. Symptoms may include impaired muscle coordination (ataxia), tremors, involuntary movements, and speech disturbances (dysarthria). (For more information on this disorder, choose "Hereditary Olivopontocerebellar Atrophy" as your search term in the Rare Disease Database.)

Individuals with De Sanctis-Cacchione syndrome will also exhibit unusually slow development, profound growth delays resulting in short stature (dwarfism), mental retardation, and/or inadequate function of the testes or ovaries (hypogonadism).

Benign skin tumors may be associated with De Sanctis-Cacchione syndrome, with onset possible before the age of five. These may include tumors that are pre-malignant or benign (non-cancerous), such as tumors made up of blood vessels (angiomas) and/or rapidly growing tumors often occurring on sun-exposed areas of the skin.

Individuals with De Sanctis-Cacchione syndrome may experience an early onset of skin cancer. For example, skin cancers such as malignant melanoma, basal cell carcinoma, and squamous cell carcinoma often occur in individuals with this disorder; the most commonly affected areas are the head, neck, and face. (For more information on these disorders, see the Related Disorders section of this report.)

In De Sanctis-Cacchione syndrome, some of the eye symptoms associated with XP may be present. These may include an extreme intolerance to light (photophobia); inflammation of the corneas of the eyes (keratitis); inflammation of the membrane that covers the white portion of the eyes (conjunctivitis); outward facing of the eyelids (ectropion); and/or inward facing of the eyelids (entropion). The severity of symptoms related to the skin and eyes may depend on the amount of exposure to ultraviolet light.


The symptoms of De Sanctis-Cacchione syndrome occur because of the body's inability to repair damage to the building blocks of genes (DNA). The damage is caused by exposure to ultraviolet light, such as rays of the sun. Everyone has certain connective tissue cells (fibroblasts) that have the ability to repair this damage through a complex process. However, the fibroblasts in people affected by De Sanctis-Cacchione syndrome lack the ability or have a reduced capacity to repair their DNA. In addition, some affected individuals' cells cannot properly repair sunlight-damaged skin.

Several forms (subdivisions) of XP have been identified, based on the capacity of the body to repair sunlight-damaged DNA. Any of the subdivisions of XP may occur in De Sanctis-Cacchione syndrome. However, the classic form of XP (xeroderma pigmentosum, stype A) or xeroderma pigmentosum, type D are most often found in association with De Sanctis-Cacchione syndrome.

De Sanctis-Cacchione syndrome is inherited as an autosomal recessive trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%.

In approximately 30 percent of the documented cases, individuals affected by De Sanctis-Cacchione syndrome have had parents who were related by blood (consanguineous). All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Investigators have determined that some cases of De Sanctis-Cacchione syndrome may be caused by disruption or changes (mutations) of a certain gene located on the long arm (q) of chromosome 10 (10q11). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Pairs of human chromosomes are numbered from 1 through 22, and an additional 23rd pair of sex chromosomes which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 10q11" refers to band 11 on the long arm of chromosome 10. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Affected Populations

De Sanctis-Cacchione syndrome is an extremely rare disorder that affects males and females in equal numbers. Although about 200 cases have been reported in Western medical literature, the exact number of cases of this disorder is not known. Onset of symptoms usually occurs during the first year of life, but in rare cases may appear during early or late childhood. Onset of some neurological symptoms may occur as late as five to 10 years of age or even in the second decade of life. De Sanctis-Cacchione syndrome was first described in the medical literature in 1932.

Standard Therapies


The diagnosis of De Sanctis-Cacchione syndrome may be confirmed when xeroderma pigmentosum is found to occur in association with one or more neurological abnormalities, mental retardation, dwarfism, and inadequate function of the testes or ovaries (hypogonadism).

Before birth (prenatal) diagnosis of XP may be confirmed through the use of a special procedure called amniocentesis. During this procedure, a sample of the fluid that surrounds the fetus is removed and tests are conducted to determine whether the fetus has XP. This procedure is usually done as part of a screening process for families with a history of XP.

A thorough clinical evaluation should be made to determine whether the other symptoms of De Sanctis-Cacchione syndrome are present (i.e., neurological abnormalities, mental retardation, dwarfism, and hypogonadism. This evaluation may include neuroimaging studies, such as magnetic resonance imaging (MRI) and computed tomography (CT) scans.

Specialized laboratory tests may be used to confirm a diagnosis of De Sanctis-Cacchione syndrome. These tests can detect defective DNA repair in white blood cells (lymphocytes), liver cells, corneal cells, and skin cells taken from people affected by De Sanctis-Cacchione syndrome. During such tests, the cells are exposed to UV radiation and/or certain cancer producing substances (carcinogens). After exposure to these substances, the defective DNA repair process of these cells becomes apparent.


In individuals with De Sanctis-Cacchione syndrome total protection of the skin from sunlight (e.g., topical sunscreens, sunglasses, double layers of clothing) is necessary to prevent the development of skin lesions and other complications (e.g., skin cancers and some neurological symptoms). Affected individuals with De Sanctis-Cacchione Syndrome must limit outdoor activities during daylight hours to avoid exposure to ultraviolet light. Avoidance of chemical carcinogens, such as those in cigarette smoke, is also recommended.

For individuals who have skin cancer, early detection and surgical removal of the lesions is essential. Regular examinations of the skin and eyes by specialists is recommended. Genetic counseling will be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.

Investigational Therapies

Information on current clinical trials is posted on the Internet at 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


For information about clinical trials sponsored by private sources, contact:

A cosmetic surgery procedure (dermabrasion), chemical peels, excision of tumors, and/or facial skin grafting have been used to treat De Sanctis-Cacchione syndrome. Dermabrasion and topical 5-fluorouracil may be effective in treating premalignant or early skin lesions. Application of a catalase cream appears to prevent tumors in some children. Ointments or creams containing vitamin A derivatives are also being investigated.

T4 endonuclease V.B. liposome encapsulated (T4N5) is an orphan drug being used to prevent the skin cancers and other skin abnormalities associated with xeroderma pigmentosum. Initial studies have shown that treatment with topical T4N5 slowed the rate of develop of skin cancers sometimes associated with De Sanctis-Cacchione syndrome. More studies are needed to determine the long-term safety and effectiveness of this drug for the treatment of xeroderma pigmentosum. For more information about T4N5, please contact:

Applied Genetics, Inc.

205 Buffalo Avenue

Freeport, New York 11520.

Various therapies are being studied for the treatment of the eye abnormalities associated with De Sanctis-Cacchione syndrome. Although surgery is often not possible because of the problems affecting the eyes, studies are being conducted in carefully selected individuals in which part of the corneas are removed and replaced (keratoplasty). Artificial tears and soft contact lenses have also been used.



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NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases

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Xeroderma Pigmentosum Society, Inc.

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Tel: (518)851-2612



Genetic and Rare Diseases (GARD) Information Center

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For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see