DeSanctis-Cacchione syndrome, as a hereditary neurocutaneous syndrome, is characterized by a combination of severe photosensitivity and neurologic deficits. It is an increasingly progressive disease that leads to early death. Therapy consists of lifelong avoidance of sunlight.
What is DeSanctis-Cacchione syndrome?
DeSanctis-Cacchione syndrome represents a special form of xeroderma pigmentosum, a hereditary hypersensitivity to sunlight. The typical symptoms of xeroderma pigmentosum are combined with severe neurological manifestations in this form. In most cases, the neurological deficits intensify over time. Already learned motor and cognitive abilities regress. In parallel, under the influence of solar radiation, skin redness, blisters and various changes on the skin develop, which can quickly degenerate into skin cancer. DeSanctis-Cacchione syndrome was first described in 1932 by De Sanctis and Caccione. It is a very rare disorder, with only about 20 cases described in the literature to date. Today, the term DeSanctis-Cacchione syndrome is no longer commonly used. The syndrome is mainly treated under the disease xeroderma pigmentosum. Approximately 30 percent of patients with xeroderma pigmentosum have been found to have developments associated with mental and motor retardation. The relationship between cutaneous and neurologic symptoms in this disease has not been clearly established.
Causes
DeSanctis-Cacchione syndrome, like classic xeroderma pigmentosum, is caused by alterations in genes that encode proteins of the DNA repair system. These proteins take care of repairing gene alterations by excising the areas of DNA where incorrect nucleotides have been inserted and replacing them with the corrected sequences. If one or more of these proteins are genetically altered, the repair process can no longer proceed successfully. Then the mutations triggered by the sun’s UV light on the exposed sites can no longer be eliminated. When UV light is absorbed, pyrimidine dimers are formed in the DNA, which leads to the incorrect insertion of nucleotides when the DNA is split during cell division. Normally, repair of these defects is not a problem with genetically intact repair proteins. A total of eight genes are responsible for coding repair proteins. The symptoms of xeroderma pigmentosum, which are exclusive to skin lesions, may be caused by mutations on one of these genes. In the special case of DeSanctis-Cacchione syndrome, a mutation of the ERCC6 gene on chromosome 10 is suspected. How the neurological deficits are caused by this mutation is still not understood. The mutation is inherited in an autosomal recessive manner. Individuals affected by the disease have two defective genes in their genome, each of which they must have inherited in equal proportions from their parents.
Symptoms, complaints, and signs
DeSanctis-Cacchione syndrome is characterized by three distinct symptom complexes. First, the symptoms from classic xeroderma pigmentosum appear. Inflammations form immediately on skin areas that have been irradiated by UV light, which change in a wart-like manner and later even degenerate into cancer. Eye changes also occur. Keratitis occurs, which subsequently leads to corneal opacification and the formation of small blood vessels in the eye. In addition, the formation of squamous cell carcinoma and melanoma of the eyes is also possible. A second complex of symptoms is characterized by varying degrees of mental retardation (oligophrenia), disorders of speech and language development. Lack of reflexes, involuntary movements, spastic paralysis, seizures, hearing loss, and microcephaly (reduced head size) also occur. Furthermore, disorders of porphyrin metabolism, growth disorders, bone maturation disorders, hypogonadism and disorders of corticosteroid metabolism occur. The symptoms already exist in infancy and become progressively more severe. This is especially true for the neurological symptoms. In contrast to classic xeroderma pigmentosum, life expectancy is even shorter in DeSanctis-Cacchione syndrome.The neurological deficits can lead to death even in childhood, while the skin problems can be largely well treated by avoiding UV radiation.
Diagnosis
The diagnosis can be made on the basis of clinical symptoms in combination with cytologic evidence of the DNA repair defect. Differential diagnosis must be made from Cockayne syndrome, cerebro-oculo-facio-skeletal syndrome (COFS), trichothiodystrophy, UV-sensitive syndrome, Rothmund-Thomson syndrome, or erythropoietic protoporphyria. Imaging techniques can detect changes within the skull such as dilated CSF spaces. EEG changes document seizures and other neurologic deficits.
When should you see a doctor?
Because DeSanctis-Cacchione syndrome leads to premature death of the affected person in most cases, the disease cannot be completely treated. However, some of the symptoms can be relieved. A doctor should be consulted if there is the formation of warts on the skin after exposure to the sun. Sudden mental retardation or speech difficulties may also indicate this syndrome. Furthermore, treatment is also necessary if the affected person suffers from hearing loss or seizures. If the convulsions are very severe and cannot be resolved, an emergency physician must be contacted. Growth disturbances also usually indicate DeSanctis-Cacchione syndrome and must be evaluated by a medical professional. Diagnosis of the syndrome is usually confirmed by various medical tests. However, first and foremost, a pediatrician should be consulted. In the case of carcinoma, surgical treatment is necessary.
Treatment and therapy
To date, causal therapy of DeSanctis-Cacchione syndrome and xeroderma pigmentosum is not yet possible. Treatment is mainly limited to protecting patients from UV radiation from the sun. Since vitamin D deficiency is also common, appropriate supplements must be administered. Vitamin A should also be taken as a preventive measure to achieve a minimum protection against UV radiation. The skin and eyes must be examined regularly for new carcinomas in order to be able to react quickly. Immediate removal of the carcinomas is absolutely necessary. Life expectancy can be prolonged by extensive protection from sunlight and rapid treatment when new skin cancer forms. In the case of classic xeroderma pigmentosum, it is thus possible to reach an age of up to 60 years. However, because the neurological deficits in a DeSanctis-Cacchione syndrome cannot be treated as well therapeutically, the life expectancy in this special form of xeroderma pigmentosum is very low.
Outlook and prognosis
Because DeSanctis-Cacchione syndrome is a hereditary disorder, it cannot be treated by causative therapy. Therefore, only symptomatic therapy is available to those affected, which can alleviate the symptoms. However, even with treatment, there is a greatly reduced life expectancy and therefore early death of the affected person. In DeSanctis-Cacchione syndrome, affected individuals suffer from severe developmental disorders and mental retardation. Skin disorders also occur, and patients also suffer from hearing difficulties and seizures. The quality of life of the affected person is therefore considerably restricted and reduced by the DeSanctis-Cacchione syndrome. Death therefore occurs in childhood, as the neurological deficits usually cannot be cured. For this reason, the treatment of DeSanctis-Cacchione syndrome is only aimed at reducing the symptoms. Patients are therefore dependent on regular examinations to detect tumors at an early stage. Likewise, most skin complaints can be reduced with the help of medication. Mental retardation and growth disorders can only be treated to a very limited extent. However, in rare cases, affected individuals can reach adulthood.
Prevention
If there is a family history of xeroderma pigmentosum, the risk for DeSanctis-Cacchione syndrome or xeroderma pigmentosum can be assessed by human genetic counseling and human genetic testing if the patient wishes to have children.Patients with DeSanctis-Cacchione syndrome can largely avoid the skin symptoms by consistent protection from UV radiation. However, this is not true for the neurologic deficits.
Follow-up
In DeSanctis-Cacchione syndrome, there are usually no special measures of aftercare available to the affected person, since the disease cannot be completely cured. Accordingly, only purely symptomatic treatment can be given, although the affected person is dependent on lifelong therapy. Since this is a genetic disease, genetic counseling can also be performed if the patient wishes to have children in order to prevent the recurrence of DeSanctis-Cacchione syndrome. The earlier the disease is diagnosed, the better the further course of the disease usually is. The treatment itself is usually accompanied by taking medication. Patients should ensure that they take the correct dosage of medication on a regular basis in order to alleviate the symptoms. Direct sunlight should also be avoided, which of course makes the daily life of the affected person much more difficult. Furthermore, patients are dependent on the help and support of family and friends, which above all can prevent psychological upsets or depression. Furthermore, regular examinations by a doctor are also necessary in order to quickly detect tumors and also to treat them.
This is what you can do yourself
The patient cannot take self-help measures that treat DeSanctis-Cacchione syndrome causally. The best self-help measure against the consequences of light hypersensitivity is to avoid UV light, especially the blazing sun, as much as possible. Since the syndrome is already noticeable in infancy and the affected persons are often mentally retarded, great attention is required on the part of family members. Children suffering from DeSanctis-Cacchione syndrome must not play in the blazing sun under any circumstances. Spending time outdoors should be avoided as much as possible, especially during midday. Passenger vehicles should be equipped with heavily darkened and UV-protected windows for the back seat. If this is not possible, car trips in good weather should be postponed as far as possible to the very early morning or late evening. Those who have their own garden should plant it with shade as much as possible to allow their child to spend time outdoors from time to time. If skin changes, such as blisters, occur after exposure to sunlight, the affected areas of the body must be observed very closely and presented to a doctor. It is not uncommon for such skin lesions to mutate into malignant tumors. Therapies as well as educational measures, which should be taken at an early stage, help against the mental retardation as well as the restricted motor skills from which the patients often suffer.
