Aims/hypothesisDominantly acting loss-of-function mutations in the ABCC8/KCNJ11 genes can cause mild medically responsive hyperinsulinaemic hypoglycaemia (HH). As controversy exists over whether these mutations predispose to diabetes in adulthood we investigated the prevalence of diabetes in families with dominantly inherited ATP-sensitive potassium (KATP) channel mutations causing HH in the proband.MethodsWe studied the phenotype of 30 mutation carriers (14 children and 16 adults) from nine families with dominant ABCC8/KCNJ11 mutations. Functional consequences of six novel missense mutations were examined by reconstituting the KATP channel in human embryonic kidney 293 (HEK293) cells and evaluating the effect of drugs and metabolic poisoning on the channels using the 86Rb flux assay.ResultsThe mutant channels all showed a lack of 86Rb efflux on exposure to the channel agonist diazoxide or metabolic inhibition. In the families, dominant ABCC8/KCNJ11 mutations were associated with increased birthweight (median + 1.56 SD score [SDS]). Fourteen children had HH and five adults were reported with HH or hypoglycaemic episodes (63%). Progression from hypoglycaemia to diabetes mellitus occurred in two individuals. Eight adults had a history of gestational diabetes in multiple pregnancies or were diabetic (diagnosed at a median age of 31 years). Within these families, none of the 19 adults who were not carriers of the ABCC8/KCNJ11 mutation was known to be diabetic.Conclusions/interpretationThe phenotype associated with dominant ABCC8/KCNJ11 mutations ranges from asymptomatic macrosomia to persistent HH in childhood. In adults, it may also be an important cause of dominantly inherited early-onset diabetes mellitus.
SUMMARY Breast size and milk secretion was studied in term and preterm infants. Breast nodules were palpable in most of the mature infants, both boys and girls. In 6 term infants without palpable breast tissue there was a high incidence of complications during late pregnancy or delivery. In light-for-gestational age infants the breast diameter was generally appropriate for gestation. None of the infants under 31 weeks' gestation had palpable breast tissue at birth, but some in the first weeks of life developed breast tissue and secreted milk. Milk had been secreted by most of the mature infants by age 7 days, and the onset was earlier in light-for-dates infants. The breast does not regress rapidly after birth. The nodules persist into the second half of the first year by which time sex differences have emerged. Clearly the growth and activity of the neonatal breast cannot be explained solely in terms of the influence of maternal hormones towards the end of gestation. Further studies on early breast tissue development may indicate the other endocrine factors concerned.
SUMMARY Histological examination of the breasts of 26 infants and young children who died suddenly between the ages of 3 weeks and 2 years was performed. The glands were composed of well formed lobules surrounded by dense interlobular stroma, while within the lobules there was looser connective tissue. The lobules contained ducts, many of which were dilated and contained secretions. Foci of extramedullary haematopoiesis were found, and in the older infants, fat was prominent within the connective tissue of the breast. Myoepithelial cells were regularly present. No sex differences in breast development at this time were noted. Newborn breast development did not regress rapidly after birth and secretory activity continued for many months in both sexes. This study shows that the human mammary gland remains active for many months after birth and may continue to grow and secrete. The findings are not consistent with the current view that breast development in infancy results from stimulation from 'pregnancy hormones.' It is more likely that the infant's own gonadal secretions are responsible.The human mammary gland has a number of well recognised phases of growth and development. In late pregnancy the fetal breast (in both sexes) is highly developed, and at birth it often secretes milk. Then at puberty the growth of the breast is usually the first sign of secondary sexual development in girls, and at this time gynaecomastia is not uncommon in boys.2 The breast reaches its maximal development during pregnancy in preparation for lactation. There is, however, another ill recognised phase of development of the human mammary gland in the first year or two of life long after the influences of pregnancy have been removed.Contrary to what has been stated3 the infant's breast does not regress rapidly after birth. Careful clinical study has shown that it often persists as a firm discrete nodule in many boys and girls during the first year of life and it may be more prominent by the age of 6 months than earlier and it is only later in infancy that the first sex differences in breast size appear: the gland being bigger then in girls.1 In prematurely born infant girls this phase of development may be even more prominent.4 After the first two years the breast bud usually remains small and barely palpable until puberty.The histological appearances of the breast in the fetus, at birth, in puberty, and pregnancy have been well described,5 6 but there are few reports on breast histology in infancy after the immediate newborn period. Also it is likely that the specimens of breast tissue that were subject to histological examination were from infants who had died in hospital after chronic illnesses. To obtain information on the natural history and histological appearances of the breast in healthy children it was decided to examine the glands of previously well infants and young children who had died suddenly. Materials and methodsThe breast bud and surmounting elipse of nipple containing skin was excised from a total of 22 cases of sudd...
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