RESUMEN
Saethre-Chotzen syndrome is one of the most common craniosynostosis syndromes. It is an autosomal dominantly inherited disorder with variable expression that is caused by germline mutations in the TWIST1 gene or more rarely in the FGFR2 or FGFR3 genes. We have previously reported that patients with Saethre-Chotzen syndrome have an increased risk of developing breast cancer. Here we have analysed a cohort of 26 women with BRCA1/2-negative hereditary breast cancer to study whether a proportion of these families might have mutations in Saethre-Chotzen-associated genes. DNA sequence analysis of TWIST1 showed no pathogenic mutations in the coding sequence in any of the 26 patients. MLPA (multiplex ligation-dependent probe amplification)-analysis also showed no alterations in copy numbers in any of the craniofacial disorder genes MSX2, ALX4, RUNX2, EFNB1, TWIST1, FGFR1, FGFR2,FGFR3, or FGFR4. Taken together, our findings indicate that mutations in Saethre-Chotzen-associated genes are uncommon or absent in BRCA1/2-negative patients with hereditary breast cancer.
Asunto(s)
Acrocefalosindactilia/genética , Pruebas Genéticas , Mutación de Línea Germinal , Proteínas Nucleares/genética , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética , Proteína 1 Relacionada con Twist/genética , Acrocefalosindactilia/epidemiología , Adulto , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Proteínas de Unión al ADN/genética , Efrina-B1/genética , Femenino , Genes BRCA1 , Genes BRCA2 , Proteínas de Homeodominio/genética , Humanos , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos/genética , Análisis de Secuencia de ADN , Factores de Transcripción/genéticaAsunto(s)
Acrocefalosindactilia/genética , Neoplasias de la Mama/genética , Mutación de Línea Germinal , Proteínas Nucleares/genética , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética , Proteína 1 Relacionada con Twist/genética , Acrocefalosindactilia/patología , Femenino , Humanos , MasculinoRESUMEN
Spring-assisted cranioplasty (SAS) has been used for the treatment of selected cases of sagittal synostosis at our unit routinely since 1998. In order to assess the long-term outcomes of this procedure, we compared the clinical data and morbidity with the pi-plasty technique, our previous standard procedure for the treatment of such children. The first 20 consecutive patients who underwent SAS for isolated sagittal synostosis with complete records, and who were 3 years old at the time of this study, were included. Twenty patients with a pi-plasty performed in the period immediately preceding the spring group acted as a control group. Cephalograms (preoperative, 1-year and 3-year), clinical examination, medical record data, medical photography, and a questionnaire (spring-group only) were used to evaluate and compare these two groups. The mean age of the spring group was 3.5 months (2.5-5.5) and the pi-plasty group 7.1 months (4-15.5) of age at surgery. There were no deaths in either group. There was a higher rate of complications in the pi-plasty group. The skull morphology was similar preoperatively in both groups but slightly different at the 3-year follow-up. The mean cephalic index (CI) in the spring group was 72 at 1 year of age and 71 at 3 years of age, indicating a minor relapse. The pi-plasty group had a mean CI of 73 at 3 years of age. The length was the same in both groups however the pi-plasty group had a lower height (mean 2 mm) and wider biparietal distance (mean 5 mm). All parents of the spring group were highly satisfied with the aesthetic results achieved, would undergo the operation again, and would recommend it to others with scaphocephaly. It was concluded that the two groups of surgery resulted in a quite similar morphologic outcome. The pi-plasty group had a cephalic index marginally closer to the normal range at 3 years of age. The spring group was superior with respect to blood loss, transfusion requirements, operative time, ICU time, recovery time, and total hospital stay.
Asunto(s)
Suturas Craneales/anomalías , Craneosinostosis/cirugía , Craneotomía/métodos , Osteogénesis por Distracción/instrumentación , Hueso Parietal/anomalías , Procedimientos de Cirugía Plástica/métodos , Pérdida de Sangre Quirúrgica , Transfusión Sanguínea , Cefalometría , Preescolar , Suturas Craneales/patología , Suturas Craneales/cirugía , Estética , Estudios de Seguimiento , Humanos , Tiempo de Internación , Estudios Longitudinales , Osteogénesis por Distracción/métodos , Padres/psicología , Hueso Parietal/patología , Hueso Parietal/cirugía , Satisfacción Personal , Complicaciones Posoperatorias , Procedimientos de Cirugía Plástica/instrumentación , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
The Saethre-Chotzen syndrome is an autosomal, dominantly inherited craniosynostosis caused by mutations in the basic helix-loop-helix transcription factor gene TWIST1. This syndrome has hitherto not been associated with an increased risk of cancer. However, recent studies, using a murine breast tumor model, have shown that Twist may act as a key regulator of metastasis and that the gene is overexpressed in subsets of sporadic human breast cancers. Here, we report a novel association between the Saethre-Chotzen syndrome and breast cancer. In 15 Swedish Saethre-Chotzen families, 15 of 29 (52%) women carriers over the age of 25 had developed breast cancer. At least four patients developed breast cancer before 40 years of age, and five between 40 and 50 years of age. The observed cases with breast cancer (n = 15) are significantly higher than expected (n = 0.89), which gives a standardized incidence ratio (SIR) of 16.80 (95% CI 1.54-32.06). Our finding of a high frequency of breast cancer in women with the Saethre-Chotzen syndrome identifies breast cancer as an important and previously unrecognized symptom characteristic of this syndrome. The results strongly suggest that women carriers of this syndrome would benefit from genetic counseling and enrolment in surveillance programs including yearly mammography. Our results also indicate that the TWIST1 gene may be a novel breast cancer susceptibility gene. Additional studies are, however, necessary to reveal the mechanism by which TWIST1 may predispose to early onset breast cancer in Saethre-Chotzen patients.
Asunto(s)
Acrocefalosindactilia/complicaciones , Neoplasias de la Mama/complicaciones , Acrocefalosindactilia/genética , Adulto , Neoplasias de la Mama/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas Nucleares/genética , Linaje , Factores de Riesgo , Proteína 1 Relacionada con Twist/genéticaRESUMEN
In the 10-year period 1986-1996, 85 patients were admitted to our unit with craniofacial injuries, 56 of whom had orbital fractures. These were studied with respect to the type of injury, type and location of fracture, presence of ocular and intracranial injury, and associated injuries to the head and body, as well as operative techniques used. Both the patient's and the surgeon's opinion on the aesthetic result were noted. The patients were also given a questionnaire about their quality of life after the injury. Road traffic crashes accounted for 31 (55%) of the injuries, falls for 9 (15%), and horse-riding for 6 (11%). The Injury Severity Score (ISS) ranged from 4 to 41 (mean 18). Twelve also had eye injuries, which resulted in complete blindness in one eye in 4 (7%). Thirty patients had 41 neurological injuries (54%), frontal contusions being the most frequent diagnosis (n = 15). Exact repositioning with rigid fixation included bone grafting to the orbit in 11 patients, and the dominating bone graft was split calvarium (n = 5). Forty-two patients completed a questionnaire, 26 of whom (64%) had no aesthetic complaints. Seven of the 42 were too disabled to work one year after the injury. Re-exploration was infrequent and the aesthetic outcome, both in the surgeon's and the patient's opinion, was good. However, the older the patient, the worse the outcome.
Asunto(s)
Traumatismos Faciales/diagnóstico , Traumatismos Faciales/cirugía , Fracturas Orbitales/diagnóstico , Fracturas Orbitales/cirugía , Adolescente , Adulto , Anciano , Trasplante Óseo , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Procedimientos Quirúrgicos Operativos , Suecia , Índices de Gravedad del Trauma , Resultado del TratamientoRESUMEN
A new surgical approach for performing the mandibular osteotomy for distraction osteogenesis is described. In order to minimize trauma to bone caused by the osteotomy - and adjacent soft tissue - caused by excessive stretching - an additional transbuccal pinhole incision is made. The shaft of the saw blade is passed through this incision. This allows a precise cut of the mandibular ramus at the planned angle and easy guidance of the saw during the procedure. The method can be used both with extraoral or intraoral distraction devices in children and adults.
Asunto(s)
Mandíbula/cirugía , Osteogénesis por Distracción/métodos , Osteotomía/métodos , Adulto , Clavos Ortopédicos , Niño , Diseño de Equipo , Humanos , Mandíbula/inervación , Nervio Mandibular/anatomía & histología , Mucosa Bucal/lesiones , Osteogénesis por Distracción/instrumentación , Osteotomía/instrumentación , Planificación de Atención al PacienteRESUMEN
It is suspected that the developmental delay in school-aged children diagnosed as infants suffering from plagiocephaly is caused by the modification of the skull form. To detect possible cognitive impairment in these children, we examined auditory ERPs to tones in infant patients. The infants with plagiocephaly exhibited smaller amplitudes of the P150 and the N250 responses to tones than healthy controls. Differences between the patients and control subjects indicate that already at this early age the presence of the plagiocephalic skull signals compromise of brain functioning. The present data suggest that most of the plagiocephalic infants have an elevated risk of auditory processing disorders. In the current study we demonstrated, for the first time, that the central sound processing, as reflected by ERPs, is affected in children with plagiocephaly.
Asunto(s)
Encéfalo/fisiopatología , Craneosinostosis/fisiopatología , Potenciales Evocados Auditivos/fisiología , Análisis de Varianza , Audiometría , Encéfalo/crecimiento & desarrollo , Estudios de Casos y Controles , Trastornos del Conocimiento/etiología , Suturas Craneales/anomalías , Craneosinostosis/complicaciones , Electroencefalografía , Electrooculografía , Movimientos Oculares/fisiología , Femenino , Hueso Frontal/anomalías , Humanos , Lactante , Masculino , Hueso Occipital/anomalías , Hueso Parietal/anomalías , Tiempo de Reacción/fisiología , Factores de Riesgo , Estadística como AsuntoRESUMEN
Extensive cytogenetic investigations of pleomorphic adenomas of the salivary glands have unequivocally demonstrated that they are cytogenetically monoclonal and are characterized by a high frequency of tumor specific chromosome abnormalities involving in particular chromosome bands 3p21, 8q12 and 12q14-15. Here we show that two radiation-associated and cytogenetically polyclonal adenomas without gross rearrangements of these breakpoints show simultaneous overexpression of the PLAG1 and HMGIC genes, i.e. the target genes of the 8q12 and 12q14-15 rearrangements in sporadic adenomas. In addition, one of the tumors expressed a cryptic CTNNB1-PLAG1 fusion transcript. Our findings strongly suggest that identical or very similar molecular mechanisms are operating during adenoma tumorigenesis irrespective of whether the tumors are cytogenetically polyclonal or whether they have non-random, tumor specific abnormalities. Cytogenetically polyclonal adenomas are thus most likely also of monoclonal origin.