| Two siblings are described whose clinical presentation of cutaneous photosensitivity and central nervous system dysfunction is strongly reminiscent of the DeSanctis-Cacchione syndrome (DCS) variant of xeroderma pigmentosum. An extensive clinical evaluation supported a diagnosis of DCS and documented previously unreported findings. in vitro fibroblast studies showed UV sensitivity that was two to three times that of normal controls. However, neither a post-UV-irradiation DNA excision-repair defect indicative of XP nor a semiconservative dna replication defect indicative of XP variant was found. Rather, a failure of rna synthesis to recover to normal levels after UV exposure was observed, a biochemical abnormality seen in cockayne syndrome (CS), one of the premature-aging syndromes with clinical UV sensitivity. These patients, therefore, clinically have XP, but their biochemical characteristics suggest CS. The reason(s) for the severe neurologic disease, in light of the relatively mild cutaneous abnormalities, is unclear. Other cases with unusual fibroblast responses to irradiation have been noted in the literature and, along with the data from our patients, reinforce the notion of the complexity of DNA maintenance and repair. ( info) |
12/82. Comparison of MRI white matter changes with neuropsychologic impairment in cockayne syndrome. The neuropsychologic function and white matter changes observed on magnetic resonance imaging (MRI) in cockayne syndrome were studied. MRI with T2-weighted sequences revealed periventricular hyperintensity and white matter hyperintensity in all 3 cockayne syndrome patients examined; in contrast, 8 age-matched controls had no periventricular or white matter hyperintensity. MRI scans were graded according to the severity of periventricular or white matter hyperintensity using a scale applied to an elderly patient population. There was no difference in the severity of MRI white matter changes in these 3 cockayne syndrome patients, 2 of whom had severe neuropsychologic functions and one a relatively milder one. There was no correlation between neuropsychologic impairment and MRI white matter changes. ( info) |
13/82. Muscle involvement in the cerebro-oculo-facio-skeletal syndrome. We report a 14-year-old male, born to consanguineous parents, with microcephaly, intracranial calcification, severe mental retardation, cataracts, optic atrophy, pigmentary retinopathy, contractures, scoliosis, and failure to thrive. His brain imaging revealed extensive basal ganglia calcifications. He has normal ultraviolet sensitivity. These features are consistent with the autosomal recessive cerebro-oculo-facio-skeletal syndrome. In addition, he has severe muscle weakness with end-stage muscle changes on biopsy. There have been few reports of muscle involvement in cerebro-oculo-facio-skeletal syndrome, and this is the first time it has been described in a cerebro-oculo-facio-skeletal patient with normal ultraviolet sensitivity. This case extends the extensive phenotypic similarities between cerebro-oculo-facio-skeletal syndrome patients with and without abnormal ultraviolet sensitivity, and highlights the cerebro-oculo-facio-skeletal syndrome in the differential diagnosis of congenital muscular dystrophies. ( info) |
14/82. Unusual neurophysiological features in Cockayne's syndrome: a report of two cases as a contribution to diagnosis and classification. To clarify the diagnostic value of neurophysiological investigations in patients with Cockayne's syndrome (CS). The study involved two patients with clinical diagnoses of classical and severe CS, who were neurophysiologically evaluated by means of: (1) multimodal visual (VEPs), brainstem auditory (BAEPs) and upper limb somatosensory (SEPs) evoked potentials; (2) electroretinography; and (3) nerve conduction and needle electromyography studies. Both patients showed multimodal evoked potential (EP) signs of central nervous system involvement that overlapped in severity and extent, and were consistent with demyelination along the central sensory pathways. Flash VEPs and SEPs were more altered than pattern VEPs and BAEPs. No signs of retinopathy or hearing loss of cochlear origin were detected. The nerve conduction and needle electromyography studies showed severe signs of sensory and motor demyelinating and axonal peripheral neuropathy. Peripheral neuropathy was clinically uncertain. There were no significant differences between the two patients. Our results show that combined multimodal EP and nerve conduction studies are diagnostically highly sensitive even in the early stage of CS, but their ability to distinguish classical and severe CS is limited. The unusual features were characterised by the absence of clinical and electrophysiological signs of otherwise common retinopathy and neurosensory hearing loss. BAEPs seem to be more useful than VEPs or SEPs in the diagnostic work-up of patients with suspected CS. ( info) |
15/82. A kindred with cockayne syndrome caused by multiple splicing variants of the CSA gene. cockayne syndrome (CS) is an autosomal recessive disorder, which is associated with abnormal UV hypersensitivity, growth retardation, and psycho-neural abnormalities. Recently, CSA protein was found to be associated with CS. We obtained mRNAs from immortal lymphoblasts derived from members of the kindred, and sequenced the CSA gene of all family members after reverse transcription (RT) of the coding region. The intact length of the CSA transcript was found in all family members except the proband with CS. Multiple abnormal splicing variant forms were revealed in all cases. No mutation was found in the sequences of the splice donor and acceptor sites of each exon in the CSA gene. UVA irradiation suppressed cell growth in the proband. There was no significant alteration of UVA sensitivity among the normal control and the family members except for the proband. These data suggest that multiple splicing variant forms of CSA mRNA, in the absence of the full-length form of the mRNA, are associated with CS. ( info) |
| cockayne syndrome is a rare autosomal recessive condition comprising microcephaly, "cachectic dwarfism" and progressive neurological degeneration. We present a 21-year-old woman who was not diagnosed with cockayne syndrome type I until she was 21 years old. family photographs demonstrated that the phenotype of cockayne syndrome did not become evident until she was 8 years old. She had severe microcephaly, micrognathia, protruding ears, dental overcrowding with caries, progressive spastic quadriparesis, and severe developmental regression. Her head computed tomography (CT) showed bilateral calcification of the globus pallidus and global atrophy. The purpose of this clinical report is to alert clinicians to the fact that the phenotypic features of cockayne syndrome may be very subtle early in the course of the disease. ( info) |
17/82. A neuropathological study of early onset cockayne syndrome with chromosomal anomaly 47XXX. We present the clinical and neuropathological findings in a female patient with early onset cockayne syndrome and a chromosomal anomaly (47XXX). The girl was the only child of healthy, unrelated parents. She was born with a birth weight of 1,930 gm. She had progeroid facial features with bilateral cataracts. A diagnosis of 47XXX was made on the basis of a chromosomal study. Physical shortness became increasingly prominent while her weight remained stationary. Psychomotor retardation was noted, and she could never sit alone. A brain CT scan showed cerebral atrophy and calcification of the basal ganglia. Cultured skin fibroblast exhibited significant sensitivity to the ultraviolet light. She died from a chest infection at the age of 7 years and 4 months. Microscopically, the renal glomeruli showed diffuse sclerotic changes with thick capillary basement membranes. A neuropathological examination revealed a very small brain (295 gm), extensive myelin deficiency, gliosis in the white matter, and calcifications in the basal ganglia, and cerebral and cerebellar cortices. The loss of both Purkinje and granular cells was noticed in the cerebellar cortex. This is the first report of a case with the cockayne syndrome and 47XXX, and the 47XXX in this patient seems to be coincidental. ( info) |
| cockayne syndrome is a rare autosomal recessive condition characterized by growth failure and multisystem progressive degeneration. We report and describe this syndrome in a Jordanian brother and sister with cockayne syndrome with first cousin parents. Clinical features included short stature, cachectic senile look, neurological deterioration, photosensitivity, mental retardation, hearing impairment and carious teeth. The phenotype is compatible with a mild variant of type I cockayne syndrome. They showed an exaggerated response to growth hormone provocation test, with slightly elevated basal insulin-like growth factor 1 levels. The radiological findings of thinning of ribs and slender femora with narrow medullary canals have not previously been reported in this syndrome. We discuss the implications of these findings. ( info) |
19/82. Two new XPD patients compound heterozygous for the same mutation demonstrate diverse clinical features. xeroderma pigmentosum (XP) and cockayne syndrome (CS) are both rare autosomal recessive disorders with defects in dna repair. They are usually distinct both clinically and genetically but in rare cases, patients exhibit the clinical characteristics of both diseases concurrently. We report two new phenotypically distinct cases of XP with additional features of CS (xeroderma pigmentosum and cockayne syndrome crossover syndrome (XP/CS)) carrying an identical mutation (G47R) in the XPD gene within the N terminus of the protein. Both patients had clinical features of XP and CS but only one fulfilled most criteria for diagnosing CS. Unusually, patient 1 developed early skin cancer, in contrast to patient 2, who never developed any malignancies. cells from both these patients have repair defects typical of xeroderma pigmentosum complementation group D (XPD) cells, but also had the phenotype of uncontrolled DNA breakage found specifically in XPD/CS cells and similarly reduced levels of TFIIH. Despite these similarities between our two patients, their clinical features are quite different and the clinical severity correlates with other cellular responses to ultraviolet irradiation. ( info) |
| cockayne syndrome manifests a spectrum of neurological dysfunction that includes medically intractable movement disorders. deep brain stimulation has not been well studied in such rare neurodegenerative conditions. In this case, stimulation of the ventral intermediate nucleus of the thalamus was used to manage severe motor symptoms in a young man with cockayne syndrome. There was a marked and progressive response to thalamic stimulation within weeks of surgery. These results suggest that patients with cockayne syndrome should be considered for deep brain stimulation to treat refractory movement disorders. ( info) |