Bannayan-Riley-Ruvalcaba syndrome: further delineation of the phenotype and management of PTEN mutation-positive cases.

Bannayan-Riley-Ruvalcaba syndrome (BRRS) is characterised by macrocephaly, intestinal hamartomatous polyps, lipomas, pigmented maculae of the glans penis, developmental delay and mental retardation. The syndrome follows an autosomal dominant pattern of inheritance. In 1997 reports on two BRRS patients with a deletion at 10q23.2-q24.1 were published. In the same year, the first two families with BRRS and a mutation of the PTEN gene were reported. Mutations in the PTEN gene have also been demonstrated in patients with Cowden syndrome (CS), which shows partial clinical overlap with BRRS, and in families with cases both of BRRS and CS. PTEN mutation positive BRRS and CS are likely to be different phenotypic presentations of the same syndrome. If BRRS and CS are one single condition, the question arises whether patients with BRRS should be screened for malignant tumours, since patients with Cowden syndrome have an increased risk of breast, endometrial, thyroid and renal cancer. We present two isolated cases and one family and confirm that BRRS and CS are allelic. Furthermore, we review the PTEN mutation positive BRRS cases, to further delineate the phenotype and to compare the cases with a genomic deletion with the cases with a point mutation. We recommend offering BRRS cases with a mutation in PTEN the same surveillance protocol for (malignant) tumours as is currently recommended for CS. In addition, we propose a yearly haemoglobin test from early infancy for the early detection of intestinal hamartomas, which are likely to give severe complications, especially in BRRS cases.

[A flow diagram for the diagnosis of acute, non-traumatic joint complaints during childhood, retrospectively applied to 115 children]. / Een stroomdiagram voor de diagnostiek van acute, niet-traumatische gewrichtsklachten op de kinderleeftijd, retrospectief toegepast bij 115 kinderen.

Acute, non-traumatic joint complaints during childhood can be caused by conditions which require a quick and adequate recognition and treatment as well as by conditions in which an expectant policy can be pursued. On the basis of certain data from the anamnesis, supplemented with findings from the physical examination it is often possible to arrive at a (probable) diagnosis. An algorithm was designed, the differential steps of which were: fever, C-reactive protein titre, involvement of the hip joint, the presence of extra-articular manifestations and the results of a full blood count, erythrocyte sedimentation rate and imaging techniques. When this algorithm was retrospectively applied to the disease data of 115 children with acute, non-traumatic joint complaints, for whom the diagnosis in the status was taken as the gold standard, the correct diagnosis was established for every single child: for 98 (85.2%) by the shortest route and for 17 (14.8%) indirectly. In the case of 4 children, use of this algorithm would have led to unnecessary laboratory investigations and/or treatment. None of the diseases requiring immediate treatment were missed.

Evaluation of 239 cases of perinatal death using a fundamental classification system.

OBJECTIVE: To classify 239 cases of perinatal death in a newly introduced classification system for underlying causes of perinatal death. DESIGN: Prospective, descriptive. SETTING: Dutch healthcare region Delft-Westland-Oostland (DWO). MATERIALS AND METHODS: In 10 years (1983-1992), all cases of perinatal death with a birthweight above 500 g (n=239) were included into the study. We used a classification model based upon the underlying cause of death using simple principles of obstetrical and neonatal pathology. A team consisting of a gynaecologist, neonatologist and pathologist classified all cases of perinatal death into seven groups to determine the "most-probable" cause of death. RESULTS: Birth trauma was seen in two cases (0.8%). Infections were seen in 16 cases (6.8%). Acute/subacute placental pathology in 77 cases (32.2%) and chronic placental pathology in 50 cases (21%). Bloodtype antagonism was seen in two cases (0.8%). Lethal congenital malformations in 55 cases (23%). Complications of pre-viable delivery in 20 cases (8.4%). Unclassifiable were 17 cases (7%): two cases could not be classified despite thorough investigation (1%) and 15 cases were lost for follow-up (6%). CONCLUSIONS: Classification of perinatal death causes by using our fundamental classification system gives insight in the possible underlying causes of death. The results of such a classification can be used as guidelines for preventive measures in the future.

Fundamental classification of perinatal death. Validation of a new classification system of perinatal death.

OBJECTIVE: To validate a newly introduced classification system for the registration of perinatal mortality. DESIGN: Descriptive. SETTING: Dutch Healthcare region Delft-Westland-Oostland (DWO). MATERIAL AND METHODS: In a 10-years period (1983-1992), all cases of perinatal death with a birthweight above 500 g (n=239) were included into the study. Six assessors: four gynaecologists and two paediatricians were asked to classify all cases using a classification model proposed by the authors. This model is based on the underlying cause of death using simple principles of obstetrical and neonatal pathology: birth trauma, infection, placenta or cord pathology, pathology of immune tolerance of mother and fetus, congenital malformation of the fetus and complications of a pre-viable delivery. Therefore, we used the term fundamental classification. The six assessors worked independently of each other in classifying all cases of perinatal death, were not involved in the original development of the system and were unaware of the results of the classification of their colleagues. Agreement beyond chance between assessors was calculated using kappa's coefficient for multiple observers and multiple test results. RESULTS: Overall kappa was 0.70 (95% confidence interval (C.I.) 0.68-0.72). Reproducibility was poor for the categories trauma and unclassifiable, fair for the categories infections and placental/cord pathology, and very good to excellent for the categories maternal immune system pathology, congenital malformations and complications of prematurity. CONCLUSIONS: The proposed system showed a good level of agreement and appeared to be simply applicable. It offers a good insight in the underlying cause of death with the possibility for recognising preventive factors in future pregnancies and will enable (inter)national comparisons in causes of perinatal death. A reliable uniform registration of perinatal death based on the underlying causes should be the basis for improvement of the quality of perinatal care.