ABSTRACT
To identify causes of death (COD) in propositi with Cornelia de Lange syndrome (CdLS) at various ages, and to develop guidelines to improve management and avoid morbidity and mortality, we retrospectively reviewed a total of 426 propositi with confirmed clinical diagnoses of CdLS in our database who died in a 41-year period between 1966 and 2007. Of these, 295 had an identifiable COD reported to us. Clinical, laboratory, and complete autopsy data were completed on 41, of which 38 were obtainable, an additional 19 had autopsies that only documented the COD, and 45 propositi had surgical, imaging, or terminal event clinical documentation of their COD. Proband ages ranged from fetuses (21-40 weeks gestation) to 61 years. A literature review was undertaken to identify all reported causes of death in CdLS individuals. In our cohort of 295 propositi with a known COD, respiratory causes including aspiration/reflux and pneumonias were the most common primary causes (31%), followed by gastrointestinal disease, including obstruction/volvulus (19%). Congenital anomalies accounted for 15% of deaths and included congenital diaphragmatic hernia and congenital heart defects. Acquired cardiac disease accounted for 3% of deaths. Neurological causes and accidents each accounted for 8%, sepsis for 4%, cancer for 2%, renal disease for 1.7%, and other causes, 9% of deaths. We also present 21 representative clinical cases for illustration. This comprehensive review has identified important etiologies contributing to the morbidity and mortality in this population that will provide for an improved understanding of clinical complications, and management for children and adults with CdLS.
Subject(s)
De Lange Syndrome/mortality , De Lange Syndrome/pathology , Adolescent , Adult , Age Factors , Autopsy , Cause of Death , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Time Factors , Young AdultABSTRACT
We report herein a case of Brachmann-de Lange syndrome complicated with congenital diaphragmatic hernia in which a NIPBL gene mutation was identified. A female infant born at 37 weeks of gestation died 134 min after delivery, even though endotracheal intubation and resuscitation were performed immediately after the scheduled caesarean operation. We diagnosed the infant with Brachmann-de Lange syndrome from her physical characteristics. An abnormal peak at the 29th exon in the translation area of the NIPBL gene was detected using denaturing high-performance liquid chromatography. In addition, a mutation of cytosine to thymine (nonsense mutation) at the 5524th base was identified using the direct sequence method. This variation was likely the cause of the syndrome.
Subject(s)
De Lange Syndrome/genetics , Proteins/genetics , Cell Cycle Proteins , Codon, Nonsense , De Lange Syndrome/mortality , Female , Hernia, Diaphragmatic/genetics , Hernias, Diaphragmatic, Congenital , Humans , Infant, Newborn , Mutation , Pregnancy , Ultrasonography, Prenatal , Young AdultABSTRACT
Se presenta el caso, un recién nacido masculino, pretérmino, que al examen físico presenta: cráneo pequeño, pestañas largas y rizadas, puente nasal plano, cejas delgadas y unidas en la línea media, hipertricosis universal, con alteraciones cardíacas; se palpa masa en región mesogástrica de 2 x 2 cm. Al 9° día presenta paro cardio-respiratorio sin respuesta a maniobras de resucitación ni otras medidas, y fallece 30 minutos después.
We reprot the case of a preterm male new born, that to the physical examination presents: small head, long and curled eyelashes, flat nasal bridge, thin and eyebrows united in the mean line, universal hypertricosis, with cardiac alterations; mesogastrica mass of 2 x 2 cm. On 9th day, present cardiorespiratory arrest and death in 30 minutes.
