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At a glance

De Sanctis-Cacchione Syndrome belongs to a group of rare inherited skin disorders called xeroderma pigmentosum that are characterized by photosensitivity, skin discolorations, eye disorders, and skin cancers. Clinical features of this medical condition include neurological abnormalities, mental retardation, dwarfism, and hypogonadism. Mental retardation, microcephaly, ataxia, areflexia, hyporeflexia represent the most common neurological abnormalities observed in individuals affected with De Sanctis-Cacchione Syndrome. The onset of the disease is noticed during the first year of life; however, it has also been observed during early or late childhood. In regards to the onset of neurological abnormalities, it occurs as late as 5 to 10 years of age or even during the second decade of life.

Synonym

Xerodermic Idiocy of De Sanctis and Cacchione; DSC Syndrome.

History

This medical condition was first described in the medical literature in 1932 by De Sanctis and Cacchione. The term “xerodermic idiocy” was coined after reporting three brothers with xeroderma pigmentosum (XP) who also presented microcephaly, mental deficiency, dwarfism, gonadal hypoplasia, progressive neurologic deterioration, deafness, and ataxia beginning at the age of 2 years.

Incidence

The exact incidence remains unknown. A review of case reports about XP surveying all the way back to 1874, when the first XP case was reported, observed that the association of XP, microcephaly and neurologic deterioration was reported only in 37 patients out of a total of 830 patients. Short stature and delayed secondary sexual development were seen in only 19 patients. Although 200 cases have been reported in Western medical literature, one may question the diagnosis based on the information presented above. Therefore, the exact number of cases of this DSC Syndrome is clearly not established. However, the incidence of xeroderma pigmentosum is estimated at 1:250,000 in the general population. The percentage of patients presenting XP and neurologic changes (as in De Sanctis-Cacchione Syndrome) represents 15 to 20%. Both genders are equally affected. There is no variation in prevalence among ethnic groups.

Genetic inheritance

It is inherited as autosomal recessive trait.

Pathophysiology

De Sanctis-Cacchione Syndrome is established as the rarest manifestations of XP with the most severe DNA repair impairment. XP causes pigmentary and atrophic skin changes as a result of a defective ability to repair normally occurring DNA changes (cross-linkage of thymidine nucleotides, called dimers) following exposure to ultraviolet (UV) light. The nucleotide excision repair mechanism, responsible in healthy individuals for elimination of these dimers, fails to excise and replace them by normal nucleotides. Early and diffuse neuronal death occurs in correlation with the degree of inability to repair DNA, which may account for the neurologic changes in this subgroup of XP. Polyneuropathy has been attributed to diffuse axonal loss in peripheral nerves in affected patients.

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