De Sanctis-Cacchione Syndrome
A number sign (#) is used with this entry because the clinical entity of de Sanctis-Cacchione syndrome can be displayed by patients with any of several different forms of xeroderma pigmentosum, although it is said to occur most often in those of complementation group A (XPA; 278700).
De Sanctis-Cacchione syndrome has also been associated with mutation in the ERCC6 gene (609413); mutations in the same gene have been found to cause Cockayne syndrome type B (CSB; 133540).
Clinical FeaturesDe Sanctis and Cacchione (1932) reported a condition, which they called 'xerodermic idiocy,' in which patients had xeroderma pigmentosum, mental deficiency, progressive neurologic deterioration, dwarfism, and gonadal hypoplasia.
Reed et al. (1965) described xeroderma pigmentosum with neurologic complications in a Caucasian brother and sister and 2 'Japanese' brothers. The patients exhibited choreoathetoid neurologic signs. Cerebral and olivopontocerebellar atrophy was found at autopsy of a Japanese case (Yano, 1950) and a Japanese-American case (Reed et al., 1969). Of the 5 patients described by Reed et al. (1969), 4 had associated neurologic features. One of the patients with the latter syndrome developed acute lymphatic leukemia at the age of 3 years. Robbins et al. (1974) suggested that death of neurons may occur more rapidly in persons with a defect in DNA repair than in normal controls.
De Weerd-Kastelein et al. (1972) found complementation when cells from classic xeroderma pigmentosum were hybridized with cells from a case of the de Sanctis-Cacchione syndrome.
Kraemer et al. (1987) noted that xeroderma pigmentosum with neurologic abnormalities was first reported in 1883 by Albert Neisser of Breslau, Germany. Neisser also discovered the bacterial cause of gonorrhea, the agent Neisseria. The patients Neisser described were 2 sibs who had XP with progressive neurologic degeneration beginning in the second decade. In a review of 830 cases of XP, Kraemer et al. (1987) found that 18% had neurologic abnormalities, including progressive mental deterioration, hyporeflexia or areflexia, and progressive deafness. Some of these patients also had dwarfism and immature sexual development.
Kanda et al. (1990) reported neuropathologic findings in 2 cases of XP group A with de Sanctis-Cacchione syndrome. Motor nerves, including those of the oculomotor system, were severely affected. Peripheral sensory nerves were also severely affected, with depletion of unmyelinated axons. The findings suggested a slowly progressive process.
Greenhaw et al. (1992) described a Hispanic brother and sister, born of consanguineous parents, with cutaneous photosensitivity and central nervous system dysfunction consistent with de Sanctis-Cacchione syndrome, except that central nervous system changes were much more striking and the cutaneous manifestations less striking than usually seen in XP. In addition, in vitro fibroblast studies showed increased UV sensitivity, but the results indicated normal DNA-excision repair and a failure of RNA synthesis, a biochemical profile consistent with Cockayne syndrome (133540) and not consistent with XP. By cell fusion complementation analysis, Itoh et al. (1996) found that these patients could be assigned to Cockayne syndrome complementation group B.
Molecular GeneticsIn the patients reported by Greenhaw et al. (1992) with a clinical phenotype of de Sanctis-Cacchione syndrome and a biochemical profile of Cockayne syndrome type B, Colella et al. (2000) identified a homozygous mutation in the ERCC6 gene (609413.0002). The results implied that the gene product from the CSB gene interacts with gene products involved in excision repair and associated with XP.