Anesthesia for a cesarean section on a pregnant patient with Cockayne syndrome: case report / Anestesia para cesárea em gestante com síndrome de Cockayne: relato de caso

Abstract Cockayne syndrome is an autosomal recessive multi-systemic disorder due to DNA repair failure. It was originally described in 1936 in children of small stature, retinal atrophy and deafness, characterized by dwarfism, cachexia, photosensitivity, premature aging and neurologic deficits. The most typical feature is described as birdlike facies: protruding maxilla, facial lipoatrophy, sunken eyes, large ears and thin nose. Difficult airway management with subglottic stenosis and risk of gastric content aspiration has been described. Although the clinical characteristics of Cockayne syndrome have been well described in pediatric publications, there is only one report in the literature on anesthesia for an obstetric patient. We report the case of a pregnant patient diagnosed with Cockayne syndrome, submitted successfully to spinal anesthesia for a cesarean section due to cephalopelvic disproportion. In view of the difficult decision between inducing general anesthesia in a patient with a likely difficult airway, or neuraxial anesthesia in a patient with cardiovascular, respiratory and neurocognitive limitations, we suggest tailored management to reach the best results for the mother and newborn.

Resumo A síndrome de Cockayne é doença multissistêmica autossômica recessiva devido à falha no reparo do DNA. Originalmente descrita em 1936 em crianças com baixa estatura, atrofia retiniana e surdez, é caracterizada por nanismo, caquexia, fotossensibilidade, envelhecimento acelerado e déficits neurológicos. O mais típico é a fácies, descrita como similar à de um pássaro: maxila proeminente, atrofia do coxim adiposo bucal, olhos profundos, orelhas grandes e nariz fino. Tem sido descrita dificuldade no manejo da via aérea com estreitamento subglótico e risco de aspiração gástrica. Embora as características clínicas da síndrome de Cockayne sejam bem relatadas em publicações pediátricas, há apenas um relato de anestesia em paciente obstétrica na literatura. Relatamos o caso de gestante com diagnóstico de síndrome de Cockayne, submetida com sucesso a raquianestesia para parto cesariano por desproporção cefalopélvica. Diante da difícil decisão entre induzir anestesia geral em paciente com provável via aérea difícil ou anestesia neuroaxial, em meio a limitações cardiovasculares, respiratórias e neurocognitivas da paciente, conduta individualizada é sugerida para alcançar os melhores resultados para a gestante e o neonato.

Advance in research on causative genes of xeroderma pigmentosum and related diseases / 中华医学遗传学杂志

Ultraviolet light(UV)-sensitive disorders refer to a group of diseases due to damages to the nucleotide excision repair mechanism which cannot effectively repair DNA damage caused by ultraviolet radiation. The inheritance pattern of such diseases, mainly including xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy, is autosomal recessive and known to involve 13 genes. As proteins encoded by such genes are involved in DNA repair and transcription pathways. There is overlap between the symptoms of such diseases, and their genotype - phenotype correlations are quite complex. To facilitate genetic and prenatal diagnosis for such diseases, a summary of the research progress is provided, which mainly focused on mutation research and genotype - phenotype correlation studies. We also propose a strategy for their genetic diagnosis based on recent findings of our group.

Clinical and molecular analysis of two Chinese siblings with Cockayne syndrome / 中华儿科杂志

<p><b>OBJECTIVE</b>Cockayne syndrome is a rare disease and difficult to be recognized. This study aimed to expand the knowledge of the clinical and molecular characteristics of the children with Cockayne syndrome (CS).</p><p><b>METHOD</b>Clinical data of two siblings with classic CS of Guangzhou Women and Children's Medical Center from July 2013 to November 2014 were obtained and analyzed. The whole DNA of peripheral blood was collected from two CS siblings and their parents. Amplification of all exons and adjacent introns for ERCC6 gene was conducted using PCR, and measurement of reaction product was performed to find mutation sites by two-way sequencing.</p><p><b>RESULT</b>Two affected siblings were males, and came from unconsanguineous parents, 7 years and 5 months old and 4 years and 8 months old, respectively. They were in treatment because of developmental and mental retardation for years. When they were younger than one year of age, their heights and weight were within normal limits. However, poor growth of height and weight and psychomotor retardation appeared after one and a half years of age, as well as skin and eye sensitivity to sunshine, hearing impairment, optic nerve atrophy, microcephaly, and deep-set eyes. The proband's height was 90.8 cm, and weight 9.1 kg, head circumference 41 cm, and chest circumference 44 cm when he was taken to hospital. The elder brother of the proband had a height of 92 cm, weight 11.2 kg, head circumference 41 cm, and chest circumference 44 cm when he was taken to hospital. When the proband was four and a half years old, ventricular enlargement, hypomyelination, and brain atrophy were detected for his elder brother at 7 years of age by cranial MRI. MRS imaging indicated that damages occurred at the left and right sides of dorsal thalamus, lobus insularis, along with the left half circle of central neurons. Symmetrical calcification on bilateral basal ganglia was found on the brain CT scan. Pathogenic compound heterozygous c. 1357C > T (p.Arg453Ter) and c. 1607T > G (p.Leu536Trp) mutations of ERCC6 gene were identified in the two siblings which were separately inherited from their unaffected parents.</p><p><b>CONCLUSION</b>CS children are usually normal at birth, however, they have severe clinical characteristics such as poor growth, psychomotor retardation, cerebral injury, microcephalus, deep-set eyes, and skin sensitivity to sunshine. ERCC6 gene mutation usually occurs, and it is easy to misdiagnose CS as cerebral palsy, primary microcephaly, and so on.</p>

Genetic analysis for a family with Cockayne syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify potential mutations among three sisters from a Chinese family suspected with Cockayne syndrome for growth and psychomotor retardation, and to offer genetic counseling and prenatal diagnosis for the family.</p><p><b>METHODS</b>G-banded karyotyping, microarray comparative genomic hybridization (CM-CGH), whole genome exon high-throughput sequencing and Sanger sequencing were employed to identify potential genetic variations for the three patients and their parents.</p><p><b>RESULTS</b>Whole exome sequencing has identified two novel missense mutations, i.e., c.1595A>G (p.Asp532Gly) and c.1607T>G (p.Leu536Trp), in exon 7 of excision repair cross-complementing rodent repair deficiency, complementation group 6 (ERCC6) gene. Sanger sequencing confirmed that all of the three sisters have inherited one of the mutations (c.1607T>G) from their father and another (c.1595A>G) from their mother.</p><p><b>CONCLUSION</b>Three sisters have all been identified as double heterozygote for mutations c.1607T>G and c.1595A>G and were diagnosed with Cockayne syndrome.</p>

Síndrome de Cockayne: relato de dois casos / Cockayne?s syndrome: report of two cases

Objetivos: Relatar casos de síndrome de Cockayne em dois irmãos, descrevendo a apresentação e a evoluçãoclínica.Descrição dos casos: Apresentam-se os casos de dois irmãos, uma menina de 8 anos e um menino de 13 anos, ambos com deficiência global do desenvolvimento, microcefalia, nanismo e facies peculiar (face triangular, microftalmia, microstomia e micrognatia). No seguimento, surgiram novos problemas, como surdez neurossensorial, hipermetropia e fotossensibilidade. Pela clínica foi sugerida a hipótese de síndrome de Cockayne, que foi confirmada por teste genético molecular.Conclusões: A síndrome de Cockayne é um distúrbio raro (1/100.000), autossômico recessivo. Seu diagnóstico pode ser moroso, pois os sinais e sintomas vão surgindo progressiva e lentamente. A conjugação dos critérios de diagnóstico pode levar anos, sendo de extrema importância a suspeição clínica.

Aims: To report cases of Cockayne syndrome in two siblings, describing the clinical presentation and evolution.Case description: We describe the cases of two siblings, an 8 years old girl and a 13 years old boy, both with global developmental disability, microcephaly, dwarfism and peculiar facies (triangular face, microphthalmia, microstomia and micrognathia). New problems emerged during follow-up: sensorineural hearing loss, hypermetropia and photosensitivity. Clinical features suggested Cockayne syndrome, which was confirmed by molecular genetictesting.Conclusions: Cockayne?s syndrome is a rare (1/100,000), recessive autosomal disorder. Its diagnosis may be delayed because the signs and symptoms arise gradually and slowly. Obtaining the diagnostic criteria can take years and clinical suspicion is extremely important.

Síndrome de Cockayne: informe de dos casos clínicos y revisión de la literatura / Cockayne syndrome: report of two clinical cases and review of the literature

Introducción: el síndrome de Cockayne es un trastorno genético autosómico recesivo, caracterizado por detención del crecimiento, retraso del desarrollo, envejecimiento prematuro y fotosensibilidad. La prevalencia es de 1/100.000 nacidos vivos; es más frecuente en el sexo masculino con una relación 3:1. Desde el punto de vista genético se han descrito dos grupos: A: mutación del gen CSA (CKN1, ERCC8) en el cromosoma 5q12; B: mutación del gen CSB (ERCC6) en el cromosoma 10q11. Presentamos dos casos diagnosticados sobre bases clínicas pero en los que carecemos de estudios genéticos. Caso 1. Niña escolar producto de padres consanguíneos quien desde el nacimiento presenta hipotonía e hipomotilidad, retardo global del desarrollo, déficit pondoestatural, cara envejecida, rasgos dismórficos, fotosensibilidad, espasticidad e hipoacusia neurosensorial y hallazgos tomográficos característicos del síndrome. Actualmente está en rehabilitación. Caso 2. Adolescente de sexo femenino con crisis convulsivas desde los dos meses, poco progreso en el desarrollo psicomotor y pondoestatural, rasgos dismórficos y cara envejecida, hipoacusia neurosensorial bilateral, distonías repetitivas; en varias oportunidades sufrió procesos infecciosos respiratorios uno de los cuales, con neumonía bilateral, la llevó a la muerte a los 14 años. Conclusión: se presentan estos casos y se revisa la literatura para llamar la atención sobre este síndrome de modo que se lo sospeche tempranamente en pacientes con retardo del desarrollo psicomotor, envejecimiento prematuro y fotosensibilidad. El diagnóstico temprano es la base para brindar consejería genética a los padres.

Introduction: Cockayne syndrome is an autosomal, recessive genetic disorder, characterized by poor growth, development impairment, premature aging, and photosensitivity. Prevalence is 1/100.000 live births, and it is more frequent in males with a ratio of 3:1. From the genetic point of view two groups have been described: Group A: mutation of the CSA gene (CKN1, ERCC8) on chromosome 5q12. Group B: mutation of the CBS gene (ERCC6) on chromosome 10q11. We report two cases that were diagnosed solely on clinical bases because no genetic studies were available. Case 1. A school-girl, born from consanguineous parents. Since birth she has suffered from hypotonia and hypomotility. She has development delay, low weight and height gain, aged face, dysmorphic features, photosensitivity, spasticity, sensorineural hearing loss, and typical findings in the CT scan. She is currently on rehabilitation. Case 2. A female teenager with seizures from the age of two months; she made slow progress in psychomotor development, and had low weight and height gain. Her features were dysmorphic and her face aged. She had bilateral sensorineural hearing loss, and repeated dystonias. She suffered from repeated respiratory infections and died, aged 14, from respiratory failure secondary to bilateral pneumonia. Conclusion: We report these two cases and a review of the literature in order to attract attention to Cockayne syndrome so that early diagnoses can be made in children with psychomotor development delay, premature aging and photosensitivity. Early diagnoses are the basis for genetic counseling.

Cockayne syndrome / 中国当代儿科杂志

Cockayne syndrome is a rare autosomal recessive disease. This paper reports a case of Cockayne syndrome confirmed by gene analysis. The baby (male, 7 years old) was referred to Peking University Third Hospital with recurrent desquamation, pigmentation and growth and development failure for 6 years, and recurrent dental caries and tooth loss for 2 years. Physical examination showed very low body weight, body length and head circumference, yellow hair, a lot of fawn spots on the face, skin dry and less elastic, and subcutaneous lipopenia. He had an unusual appearance with sunken eyes, sharp nose, sharp mandible, big auricle and dental caries and tooth loss. Crura spasticity and ataxia with excessive tendon reflexion, and ankle movement limitation while bending back were observed. He had slured speech. The level of serum insulin like growth factor I was low, and the results of blood and urinary amino acid analysis suggested malnutrition. The results of blood growth hormone, thyroxin, parathyroxin, liver function, renal function, lipoprotein profile and blood glucose and electrolytes were all within normal limit. An electronic hearing examination showed moderate neural hearing loss. The sonogram of eyes revealed small eye axis and vitreous body opacity of right side. MRI of brain revealed bilateral calcification of basal ganglia and generalized cerebral and cerebellar atrophy, and brainstem and callus were also atrophic. Genetic analysis confirmed with CSA gene mutation. So the boy was definitely diagnosed with Cockayne syndrome. He was discharged because of no effective treatment.

Werner syndrome: a case report and review of literature

Werner's syndrome is a rare inherited disorder characterized by short stature, sclerosed skin, cataract and premature aging of the face. The disease involves multiple systems of the body and some of the abnormalities may cause life threatening complications such as myocardial infarction and malignancy. We report a case of this rare disorder

Infantile onest of cockayne syndrome without photosensitivity in a Tunisian Girl

Cockayne syndrome is a rare autosomal recessive disorder with dwarfism, mental retardation, and otherwise clinically heterogeneous features. Classically, the onset of Cockayne syndrome starts in the second year of life. The failure of RNA synthesis to recover to normal rates after UV-C irradiation provides a useful diagnostic test and the clinical feature that correlates most strongly with defective RNA synthesis is photosensitivity. To report an unusual case of Cockayne Syndrome. A case of a five-year-old girl with Cockayne with an onset in early infancy the girl and without photosensitivity is presented. The diagnosis was confirmed by the failure of RNA synthesis to recover to normal rate after UV-C irradiation. The patient died at the age of 6 of pneumonia. Although rare, Cockayne syndrome may be presented without photosensitivity and had an early onset

Cerebro-oculo-facio-skeletal syndrome: A case report / 소아과

The Cerebro-oculo-facio-skeletal (COFS) syndrome is a rare autosomal recessive disorder characterized by multiple abnormalities that involve the brain, face, eyes, and extremities. COFS syndrome is regarded as a degenerative disorder of the brain and spinal cord caused by a mutation of the DNA repair genes. We report on an 8-month-old girl with COFS syndrome who exhibited growth and developmental delay, hypotonia, microcephaly, nystagmus, cleft palate, widely separated nipples, inguinal hernia, camptodactyly, and rocker-bottom feet with vertical talus.

A Case of Cockayne Syndrome with Focal Segmental Glomerulosclerosis

Cockayne syndrome is a rare autosomal recessive disorder characterized by cachectic dwarfism, mental retardation, loss of facial subcutaneous adipose tissue, microcephaly and photosensitive dermatitis. It is associated with renal abnormalities characterized by hyalinization of glomeruli, atrophy of tubules and interstitial fibrosis. To our knowledge, this is the first report of a case of Cockayne syndrome with FSGS in Korea. A 7-year old boy was admitted for evaluation of hypertension and proteinuria, which were detected 2 month ago. He was followed for short stature(<3 percentile), mental retardation(IQ 55), strabismus and dental caries since 3 years ago. He also showed microcephaly, a bird-like face and relatively large hands and feet. Laboratory findings showed decreased creatinine clearance(CCr 76.1 mL/min/1.73m2) and proteinuria(1,548 mg/day). Renal biopsy demonstrated focal segmental glomerulosclerosis of the hilar type with large hyaline deposits, moderate tubular atrophy and interstitial fibrosis. His cardinal features, mental retardation, and renal biopsy findings were consistent with Cockayne syndrome. We report here a very rare case of Cockayne syndrome with FSGS presenting with proteinuria and hypertension.

siRNA-mediated silencing of Cockayne Cyndrome group B gene potentiates radiation-induced apoptosis and antiproliferative effect in HeLa cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cockayne syndrome (CS) is a rare human genetic disorder characterized by increased UV sensitivity, developmental abnormalities and premature aging. Cells isolated from individuals with CS have a defect in transcription-coupled DNA repair. Despite the repair defect, there is no any increased risk of spontaneous or UV-induced cancer for CS individuals. The strategy of RNA interfering was used here to explore the potential radiosensitizing and anticancer activity of targeting CS group B (CSB) gene.</p><p><b>METHODS</b>The vectors encoding CSB-specific siRNAs were constructed by inserting duplex siRNA encoding oligonucleotides into the plasmid P(silencer TM 3.1). The cell lines expressing the CSB-siRNA were generated from HeLa cells transfected with the above vectors. Colony-forming ability was used to assay cell survival. Cell cycle was analyzed by FACScan flow cytometry. The apoptosis was measured by detecting the accumulation of sub-G(1) population as well as by fluorescence staining assay. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to semi-quantify mRNA expression. Protein level was detected by Western blotting analysis.</p><p><b>RESULTS</b>Two constructs encoding CSB-specific siRNA were generated, both of them resulted in remarkable suppression on CSB expression in HeLa cells, and led to an increased sensitivity to (gamma-ray and UV light. siRNA-mediated silencing of CSB decreased cell proliferation rate, increased spontaneous apoptosis as well as the occurrence of UV- or cisplatin-induced apoptosis by 2 to 3.5 fold. A significant S phase blockage and a remarkable reduction of G(1) population were induced in control HeLa cells at 18 hours after being exposed to 10 J/m(2) of UV light. The S phase blockage was also observed in UV-irradiated CSB-siRNA transfected HeLa cells, but the extent of increased S phase population was lower than that in the UV-irradiated control cells. No or a relative weak reduction on G(1) phase population was observed in UV-irradiated CSB-siRNA transfected HeLa cells. In addition, siRNA-mediated silencing of CSB promoted the elimination of G(2)/M phase cells after UV light radiation.</p><p><b>CONCLUSIONS</b>siRNA-mediated silencing of CSB causes cells to proliferate more slowly, sensitize cells to genotoxicants, and modify UV radiation-induced cell cycle changes. siRNA-mediated inactivation of CSB could be an attractive strategy for ameliorating cancer therapy, which can be fulfilled via the combination of gene therapy and sensitization of radiotherapy or chemotherapy.</p>

Progeria / Progeria

La progeria o síndrome de Hutchinson-Gilford es un síndrome poco frecuente. Consiste en la aparición de signos de envejecimiento en niños entre su primer y segundo año de vida. La mayoría de los casos de progeria son esporádicos, lo cual plantea la posibilidad de un patrón de herencia autosómico dominante por mutación de novo. El diagnóstico diferencial de esta entidad debe plantearse con cualquiera de los otros síndromes progeroides descritos en la literatura. Se presenta una revisión actualizada sobre el tema haciendo énfasis en la aproximación diagnóstica del cuadro

Cockayne syndrome.

We report four cases of Cockayne Syndrome in a family of seven children. Apart from the usual clinical and laboratory features, sparse eye lashes and high arched palate in two patients, conjunctival and corneal edema in one, and proximal muscle weakness in one patient were noticed as additional findings.

Cockayne syndrome: report of a Brazilian family with confirmation of impaired RNA synthesis after UV-irradiation

A síndrome de Cockayne (CS) é uma desordem autossômica recessiva caracterizada por nanismo, déficit de crescimento, deterioraçäo neurológica, fotossensibilidade e uma progressiva aparência facial característica. Neste artigo relatamos a primeira família brasileira com CS, cujo diagnóstico foi confirmado pela demonstraçäo de uma síntese diminuída de RNA na cultura de fibroblastos expostos à radiaçäo ultravioleta. Apesar do curso progressivo da doença e da inexistência de um tratamento efetivo, o diagnóstico faz-se muito importante, pois a família pode se beneficiar do aconselhamento genético e/ou do diagnóstico pré-natal.