RESUMEN
Osteopathia striata congenita with cranial sclerosis (OSCS) is a skeletal dysplasia caused by germline deletions of or truncating point mutations in the X-linked gene WTX (FAM123B, AMER1). Females present with longitudinal striations of sclerotic bone along the long axis of long bones and cranial sclerosis, with a high prevalence of cleft palate and hearing loss. Intellectual disability or neurodevelopmental delay is not observed in females with point mutations in WTX leading to OSCS. One female has been described with a deletion spanning multiple neighbouring genes suggesting that deletion of some neighbouring loci may result in abnormal neurodevelopment. In this cohort of 13 females with OSCS resulting from deletions of WTX, a relationship is observed where deletion of ARHGEF9 and/or MTMR8 in conjunction with WTX results in an additional neurodevelopmental phenotype whereas deletion of ASB12 along with WTX is associated with a good neurodevelopmental prognosis.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Eliminación de Gen , Discapacidad Intelectual/genética , Osteosclerosis/genética , Proteínas Supresoras de Tumor/genética , Cromosomas Humanos X/genética , Estudios de Cohortes , Análisis Mutacional de ADN/métodos , Femenino , Genes Ligados a X/genética , Factores de Intercambio de Guanina Nucleótido/genética , Humanos , Mutación Puntual , Factores de Intercambio de Guanina Nucleótido RhoRESUMEN
CHARGE (coloboma of the eye, heart defects, choanal atresia, retarded growth and development, genital hypoplasia and ear anomalies and/or hearing loss) syndrome is a rare genetic, multiple-malformation syndrome. About 80% of patients with a clinical diagnose, have a mutation or a deletion in the gene encoding chromodomain helicase DNA-binding protein 7 (CHD7). Genotype-phenotype correlation is only partly known. In this nationwide study, phenotypic characteristics of 18 Danish CHD7 mutation positive CHARGE individuals (N = 18) are presented. We studied patient records, clinical photographs, computed tomography, and magnetic resonance imaging (MRI). Information was not available for all traits in all subjects. Therefore, the results are presented as fractions. The following prevalence of cardinal symptoms were found: coloboma, 16/17; heart defects, 14/18; choanal atresia, 7/17; retarded growth and development, 11/13; genital abnormalities, 5/18; ear anomalies, 15/17 and sensorineural hearing loss, 14/15. Vestibular dysfunction (10/13) and swallowing problems (12/15) were other frequent cranial nerve dysfunctions. Three-dimensional reconstructions of MRI scans showed temporal bone abnormalities in >85%. CHARGE syndrome present a broad phenotypic spectrum, although some clinical features are more frequently occurring than others. Here, we suggest that genetic testing for CHD7 mutation should be considered in neonates with a specific combination of several clinical symptoms.
Asunto(s)
Síndrome CHARGE/patología , ADN Helicasas/genética , Proteínas de Unión al ADN/genética , Estudios de Asociación Genética , Adolescente , Enfermedades del Desarrollo Óseo/genética , Enfermedades del Desarrollo Óseo/patología , Síndrome CHARGE/genética , Niño , Preescolar , Coloboma/genética , Coloboma/patología , Dinamarca/epidemiología , Discapacidades del Desarrollo/genética , Discapacidades del Desarrollo/patología , Oído Externo/anomalías , Oído Externo/patología , Asimetría Facial/genética , Asimetría Facial/patología , Femenino , Pérdida Auditiva Sensorineural/genética , Pérdida Auditiva Sensorineural/patología , Cardiopatías Congénitas/genética , Cardiopatías Congénitas/patología , Humanos , Lactante , Masculino , Anomalías de la Boca/genética , Anomalías de la Boca/patología , Mutación , Estudios Retrospectivos , Anomalías Urogenitales/genética , Anomalías Urogenitales/patologíaRESUMEN
A 34-year-old Caucasian woman with cleidocranial dysplasia (CCD) and a known family history of CCD was referred for an ultrasound examination in the first trimester of her second pregnancy. Molecular genetic analysis of the RUNX2 gene was non-informative. A routine 2D ultrasound examination carried out at a local hospital at gestational age 12 weeks showed no signs of CCD. A 3D ultrasound examination in week 15+4 showed a fetus with typical CCD features including large fontanelles, lack of nasal bones, clavicles without the typical S-form, as well as severe delay in calvarial ossification, especially in the midline. Serial 3D ultrasound examinations during pregnancy confirmed the diagnosis, and over time the manifestations became even more distinct. The diagnosis was clinically confirmed at birth. This case suggests that the typical craniofacial CCD traits, including wide unmineralized areas in the calvarial midline and missing nasal bones, are easily recognizable using 3D ultrasound as early as in week 15.
Asunto(s)
Displasia Cleidocraneal/diagnóstico por imagen , Ultrasonografía Prenatal , Adulto , Displasia Cleidocraneal/genética , Femenino , Humanos , EmbarazoRESUMEN
OBJECTIVE: Early prenatal diagnosis of cleidocranial dysplasia (CCD) in a case in which molecular genetic analysis of the RUNX2 gene was non-informative. METHODS: 2D ultrasound examination. RESULTS: At week 13+6, a 2D ultrasound examination revealed a fetus with severely delayed ossification of the vertebral spine. The clavicles were barely seen and the calvarial bones were significantly less ossified than expected for gestational age. The fetus had otherwise normal anatomy and biometry. Serial ultrasound examinations during pregnancy confirmed the diagnosis, but the manifestations became less distinct. The diagnosis was confirmed clinically at birth. CONCLUSION: This case illustrates an early easily recognizable pattern of severely delayed ossification of the vertebral spine, which is probably a characteristic of CCD.