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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurological manifestations of xeroderma pigmentosum, a rare autosomal recessive neurocutaneous syndrome, are variable. The association with progressive mental retardation, usually with onset in childhood, is well known. We present a case of x.p. with progressive presenile dementia. This combination has, to our knowledge, not yet been reported in the literature. Although no hints on another aetiology have been found, the coincidental combination of x.p. with M. Alzheimer has to be taken into consideration. CT scan and MRI showed a marked cerebral atrophy.
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PMID:[Presenile dementia in xeroderma pigmentosum]. 174 55

Photosensitive genodermatoses associated with established defects of DNA repair currently include the autosomal recessive diseases xeroderma pigmentosum (XP), Cockayne's syndrome (CS), trichothiodystrophy (TTD), and Bloom's syndrome (BS). XP is a heterogeneous disorder associated with defective excision repair or daughter strand repair of ultraviolet (UV)-induced DNA damage. It is characterized by cutaneous and ocular abnormalities predominantly on sun-exposed sites and in some cases, neurological features resulting from progressive neuronal loss. Skin involvement includes easy sunburning, pigmentary abnormalities, telangiectasia, dryness, scarring, and susceptibility to multiple benign and malignant neoplasms. In CS, defective repair of actively transcribing DNA is clinically associated with acute photosensitivity, growth retardation, demyelinating neurological abnormalities, and pigmentary retinal degeneration, but without increased cancer susceptibility. TTD is characterized by sulphur-deficient brittle hair, variable growth delay, mental retardation, ichthyosis, and in some cases photosensitivity. Although in some patients there is a deficiency of DNA excision repair identical to that in certain xeroderma pigmentosum patients, no increased cancer risk is present in trichothiodystrophy. In BS, deficient cellular DNA ligase is associated with congenital telangiectasia, photosensitivity, growth retardation, immune deficiency, increased susceptibility to infection, and predominantly internal rather than cutaneous malignancy. Immunological factors may at least determine the varying susceptibility to malignancy of these conditions.
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PMID:DNA repair deficient photodermatoses. 220 44

Multi-modality evoked potentials in two cases, who were siblings, of De Sanctis-Cacchione syndrome were reported. The case 1, who was elder sister of the case 2, was a 25-year-old female. And the case 2 was a 23-year-old female. They have the history of consanguinity. They were first noted to have skin erythema on exposure to sunlight, and a diagnosis of xeroderma pigmentosum was made. At the childhood neurological manifestation, such as mental retardation, deafness and muscular weakness developed gradually. The case 2, who was a elder sister, was operated on for squamous cell carcinoma of the eyelid at the age of 20 and 21 years old. Motor conduction velocity obtained from lower limbs were severely reduced and that from upper limbs were moderately delayed. Sensory conduction velocity of median nerve were severely diminished. Auditory brainstem responses (ABR) of the case 1 showed the prolongation in interpeak latency of I-V. ABR of the case 2 could not be obtained. N19 and N13 of short-latency somatosensory evoked potentials (SSEP) to median nerve stimulation with case 2 could not be obtained too. N13-N19 latency of case 1 was remarkably prolonged compared to the normal subjects. Central motor conduction time (CMCT) was studied in case 2 by using the magnetic stimulator. CMCT of case 2 was within the upper limit of normal control. Interpeak latency of I-V in ABR represents the brainstem dysfunction in auditory pathway, and interpeak latency of N13-N19 in SSEP was recognized as central conduction time from medial lemniscus to primary sensory area of cortex. So the prolongation of these interpeak latency in this cases may mean the dysfunction in the central nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Electrophysiological studies in siblings of De Sanctis-Cacchione syndrome]. 261 4

Xeroderma pigmentosum associated with neurological abnormalities is a less familiar neurocutaneous disorder. In this report, 35 patients with group A xeroderma pigmentosum were assessed for neurological complications. Of these, 17 showed microcephaly and 24 mental retardation. Of 25 patients over 7 years of age, 22 had sensorineural deafness and 12 showed spinocerebellar signs such as nystagmus, dysarthria, tremor and ataxia, while none below 7 years of age had such neurological complications. Thirty-five EEG studies were performed on 29 patients, and 15 showed intermittent spindles of grouped theta waves with abnormal slow background activity and a poorly developed alpha rhythm, suggesting immature brain development or a regression from normal brain function in many areas including the diencephalon. Twenty-six patients were examined by cranial CT scan, of whom 20 showed abnormal CT findings such as ventricular dilatation, diffuse cortical atrophy, and marked thickening of the calvarial bones. The incidence of abnormal EEG and CT findings increased with advancing age in accordance with the development of neurological complications in the CNS, thus suggesting a chronic progressive degenerative disease.
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PMID:EEG and CT abnormalities in xeroderma pigmentosum. 281 76

Xeroderma pigmentosum is an unusual neurocutaneous disorder. Recent studies have classified patients with xeroderma pigmentosum into 10 groups by somatic cell hybridization methods. In this report we describe 32 patients with Group A xeroderma pigmentosum, including 1 patient with an atypical case, who were assessed for neurological complications. Of these patients, 17 had microcephaly, 13 short stature, and 21 mental retardation. In patients over 7 years of age, sensorineural deafness and spinocerebellar signs such as nystagmus, dysarthria, tremor, and ataxia were frequently observed; no patients below 7 years of age had such neurological complications. Electroencephalographic studies revealed abnormal slow and low voltage background activity. Two patients had focal abnormal discharges, one of whom developed versive seizures. Cranial computed tomographic scans revealed abnormalities, including ventricular dilatation, cerebral atrophy, cerebellar and brainstem atrophy, and cranial bone thickening. A patient with an atypical case of Group A xeroderma pigmentosum had less skin and neurological involvement, and higher levels of postultraviolet colony-forming ability and host cell reactivation than did a typical Group A case. It is possible that these less severe cytological findings are responsible for the less severe skin lesions and neurological complications noted clinically.
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PMID:Neurological manifestations in xeroderma pigmentosum. 374 Aug 15

Heterozygous carriers of an ataxia-telangiectasia (A-T), Fanconi anemia (FA), or xeroderma pigmentosum (XP) gene may be predisposed to some of the same congenital malformations or developmental disabilities that are common among homozygotes. To test this hypothesis, medical records, death certificates, and questionnaires from 27 A-T families, 25 FA families, and 31 XP families were reviewed. Eleven XP blood relatives (out of 1,100) were found with moderate or severe unexplained mental retardation, a significant excess compared to the FA and A-T families (3/1,439). There were four microcephalic XP blood relatives and none in the FA or A-T families. In the A-T families, idiopathic scoliosis and vertebral anomalies were in excess, while genitourinary and distal limb malformations were found in the FA families. A-T, FA, or XP heterozygotes may constitute an important proportion of individuals at risk for specific malformations or developmental abnormalities.
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PMID:Congenital malformations and developmental disabilities in ataxia-telangiectasia, Fanconi anemia, and xeroderma pigmentosum families. 712 32

Xeroderma pigmentosum (XP) occurs with high frequency in Egypt and a continuation of our field studies has identified representatives of the 3 major complementation groups A, C, and variant. Group A patients, with one exception, showed very early onset of sun sensitivity and development of skin cancers, and microcephaly and mental retardation. The exceptional group A patient was 35 yr old, with normal stature and intelligence who had 2 normal children. DNA repair was as low in his cells as in other group A cases. Group C patients showed a slightly slower onset of sun sensitivity and had no central nervous system disorders. The variants showed later onset of sun sensitivity and no skin cancers evident at the time of observation (about 20 yr of age). No sun sensitivity was present in the 25 heterozygotes we observed, nor reportedly in the additional 60 not yet observed. This indicates that only homozygosity for XP genes increases risk of skin cancer. Cell cultures from both normal persons and these XP patients reached in vitro "senescence" at similar passage levels. Groups A and C appear to have lost different major gene products that are involved in the excision of UV damage from DNA, but the residual repair in XP-C cells facilitates more recovery of DNA synthesis than in other groups. This may contribute to the higher in vitro survival in culture and milder clinical symptoms in group C as compared to group A. XP variants appear to have lost a gene product that permits normal cells to replicate, uninterrupted by DNA damage, and consequently synthesize DNA in smaller pieces than normal.
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PMID:Xeroderma pigmentosum patients from Egypt: II. Preliminary correlations of epidemiology, clinical symptoms and molecular biology. 725 63

Mutations in the human XPD gene result in a defect in nucleotide excision repair of ultraviolet damaged DNA and cause the cancer-prone syndrome xeroderma pigmentosum (XP). Besides XP, mutations in XPD can cause another seemingly unrelated syndrome, trichothiodystrophy (TTD), characterized by sulfur-deficient brittle hair, ichthyosis, and physical and mental retardation. To ascertain the underlying defect responsible for TTD, we have expressed the TTD mutant proteins in the yeast Saccharomyces cerevisiae and determined if these mutations can rescue the inviability of a rad3 null mutation. RAD3, the S. cerevisiae counterpart of XPD, is required for nucleotide excision repair and also has an essential role in RNA polymerase II transcription. Expression of the wild type XPD protein or the XPD Arg-48 protein carrying a mutation in the DNA helicase domain restores viability to the rad3 null mutation. Interestingly, the XPD variants containing TTD mutations fail to complement the lethality of the rad3 null mutation, strongly suggesting that TTD mutations impair the ability of XPD protein to function normally in RNA polymerase II transcription. From our studies, we conclude that XPD DNA helicase activity is not essential for transcription and infer that TTD mutations in XPD result in a defect in transcription.
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PMID:Lethality in yeast of trichothiodystrophy (TTD) mutations in the human xeroderma pigmentosum group D gene. Implications for transcriptional defect in TTD. 762 61

Trichothiodystrophy (TTD), an autosomal recessive disorder characterized by sulfur-deficient brittle hair, identifies a group of genetic disorders with an altered synthesis of high-sulfur matrix proteins and a defect in excision repair of ultraviolet damage in fibroblasts of most TTD patients. In contrast to patients with xeroderma pigmentosum (XP), TTD patients do not have an increased frequency of skin cancers. TTD patients may be grouped into four categories: 1) those without photosensitivity and without a defect in excision repair of UV damage; 2) those without photosensitivity and with an excision-repair defect in the same gene as in XP-D (complementation group D); 3) those with photosensitivity and with the XP-D repair defect; 4) those with photosensitivity and with a repair defect distinct from that in XP-D. We present a brother and sister in the third category of TTD. Clinically, the patients have brittle hair, short stature, ichthyosis, photosensitivity, nail and dental dysplasias, cataracts, mental retardation, and pyramidal tract abnormalities. Diagnosis was made by hair mount, which shows the characteristic banding pattern with polarizing microscopy, and by hair amino acid analysis, which demonstrated decreased high-sulfur matrix proteins. Fibroblasts cultured from skin biopsies had a marked DNA excision repair defect similar to the repair defect seen in XP-D. We have documented a unique dysmyelinating disorder on magnetic resonance imaging of the brain that might explain their mental retardation, marked hyperactivity, and neurologic deficits. Following the discovery that the human excision repair cross complementing rodent ultraviolet group 2 (ERCC2) gene is able to correct the ultraviolet sensitivity of XP-D cell strains, the ERCC2 cDNA from previous TTD patients was sequenced and shows frameshifts, deletions and point mutations in the ERCC2 gene. Molecular analysis of our patients is in progress. Molecular analysis of the defects in ERCC2 in clinically distinct patients with XP,XP/Cockayne's syndrome, and TTD may provide insight into the molecular mechanisms of these genetically related but clinically distinct disorders.
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PMID:Trichothiodystrophy: clinical spectrum, central nervous system imaging, and biochemical characterization of two siblings. 796 80

The sun-sensitive, cancer-prone genetic disorder xeroderma pigmentosum (XP) is associated in most cases with a defect in the ability to carry out excision repair of UV damage. Seven genetically distinct complementation groups (i.e., A-G) have been identified. A large proportion of patients with the unrelated disorder trichothiodystrophy (TTD), which is characterized by hair-shaft abnormalities, as well as by physical and mental retardation, are also deficient in excision repair of UV damage. In most of these cases the repair deficiency is in the same complementation group as is XP group D. We report here on cells from a patient, TTD1BR, in which the repair defect complements all known XP groups (including XP-D). Furthermore, microinjection of various cloned human repair genes fails to correct the repair defect in this cell strain. The defect in TTD1BR cells is therefore in a new gene involved in excision repair in human cells. The finding of a second DNA repair gene that is associated with the clinical features of TTD argues strongly for an involvement of repair proteins in hair-shaft development.
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PMID:A new nucleotide-excision-repair gene associated with the disorder trichothiodystrophy. 821 12


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