Summary. We report on nine children with Shwachman–Diamond syndrome (SDS), eight of whom had clonal abnormalities of chromosome 7. Seven children had an isochromosome 7 [i(7)(q10)] and one a derivative chromosome 7, all with an apparently identical (centromeric) breakpoint. Children with SDS are predisposed to myelodysplasia (MDS) and acute myeloid leukaemia (AML) often with chromosome 7 abnormalities. Allogeneic transplants have been used to treat these children, however, they are a high‐risk transplant group and require careful evaluation. Three of the children were transplanted but only one survived, who to our knowledge remains the longest surviving SDS transplant patient (4·5 years +). The six non‐transplanted children are well. In classic MDS, chromosome 7 abnormalities are associated with rapid progression to acute leukaemia; however, we present evidence to suggest that isochromosome 7q may represent a separate disease entity in SDS children. This is a particularly interesting finding given that the SDS gene has recently been mapped to the centromeric region of chromosome 7. Our studies indicate that i(7)(q10) is a relatively benign rearrangement and that it is not advisable to offer allogeneic transplants to SDS children with i(7)(q10) alone in the absence of other clinical signs of disease progression.
Early respiratory mechanics have been reported to predict outcome in newborns with respiratory failure. However, it remains unknown whether measurements of pulmonary function add significantly to the predictive value of more readily available variables The present study was designed to answer this question. Passive respiratory system mechanics were measured by an airway occlusion technique in 104 ventilator-dependent premature infants between 6 and 48 hours of life and corrected for infant size. A ventilation index [FiO2 x mean airway pressure (MAP)] was calculated at the time of pulmonary function testing. Poor outcome was defined as death from respiratory failure or need for supplemental oxygen at 28 days. Stepwise logistic function regression examined whether ventilation index and respiratory mechanics added predictive power over and above birthweight. Five infants died, and 45 patients required supplemental oxygen at 28 days. Birthweight was a strong predictor and would have entered the logistic model first in any case. Ventilation index added significantly to the predictive model (P = 0.038). Respiratory system conductance (P = 0.15) and compliance (P = 0.93) entered on the third and last step, respectively. We conclude that in premature infants with respiratory failure, birthweight is a strong predictor of outcome. Early ventilator requirements but not respiratory system mechanics, add significantly to this predictive model.
The proband, first of the twins, weighed 2430 g (> 10th centile), the co-twin weighing 2130 g (<10th centile). The most striking features on examination of the proband were macroglossia, moderate sized exomphalos, and widely spaced nipples. No indentation of the ear lobules was noted. Early hypoglycaemia was managed with dextrose infusion, and the exomphalos was corrected within the first 24 hours of life. The second twin was of normal appearance but was small for gestational age. There were no neonatal problems. Examination of the parents did not reveal any ear creases, posterior pits, or divarication of rectus muscles, and they were not of large birthweight.After initial catch up growth the second twin's growth variables at the age of 18 months continued along the 10th centile, and developmental assessment at that age was within normal limits. The proband had feeding difficulties related to her macroglossia, and partial glossectomy was eventually performed at the age of 17 months. Despite these problems her growth has continued along the 50th centile for height, weight, and occipitofrontal head circumference. At the age of 18 months her development was delayed by six months. No abdominal mass was detected at any time.Investigations to determine zygosity showed both twins to be of blood groups A, rr. They were identical when typed for Kell, Fya, Jka, P1, and MNS. In the HLA system both were A 3, 30, B7, 13, and CW 7. The parents were also typed and the final probability of monozygosity was 0 995. Chromosomal preparations were made from cells cultured from peripheral blood of both twins and stained to reveal both C and G bands. No differences were observed in C band polymorphisms, thus supporting monozygosity, and no abnormality was detectable on any chromosome of either child. Chromosome 11 was particularly closely examined on prometaphase cells.
Discussion
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