Haploinsufficiency of ANKRD11 (16q24.3) Is Not Obligatorily Associated with Cognitive Impairment but Shows a Clinical Overlap with Silver-Russell Syndrome.

Microdeletions in 16q24.3 are associated with intellectual disability and a specific phenotype, e.g. short stature and a prominent forehead. The 16q24.3 microdeletion syndrome shows a broad phenotypic overlap with the KBG syndrome, which is caused by mutations within the ANKRD11 gene. Furthermore, both KBG and the 16q24.3 microdeletion syndromes show clinical findings reminiscent of Silver-Russell syndrome (SRS), an imprinting disorder characterized by severe primordial growth retardation. In a cohort of patients referred as SRS, we previously identified a 16q24.3 deletion, but at that time, only patients with larger imbalances in 16q24.3 and intellectual disability had been published. Considering the recent description of the ANKRD11 gene as the causative factor for the 2 16q24.3-associated disorders, we now classified our patient as a 16q24.3 microdeletion syndrome patient exhibiting some characteristic features but normal intelligence. Our case illustrates the broad clinical spectrum associated with microdeletions, and we confirm that the 16q24.3 microdeletion syndrome is a further microdeletion syndrome with very variable expressivity. Indeed, our case is the first 16q24.3 patient of normal intelligence, but we assume that this variant is present in further mentally healthy probands which have not yet been tested. In conclusion, the detection of the 16q24.3 deletion in a proband of unremarkable intellectual capacities once again illustrates the need to perform molecular karyotyping in dysmorphic patients with normal intelligence.

Down's syndrome in diabetic patients aged <20 years: an analysis of metabolic status, glycaemic control and autoimmunity in comparison with type 1 diabetes.

AIMS/HYPOTHESIS: Intellectual impairment in individuals with Down's syndrome and diabetes mellitus potentially limits the quality of diabetic control. In addition, these patients are at risk of having immunological abnormalities. The present study compared metabolic status and concomitant diseases in young (<20 years old) Down's syndrome patients with diabetes vs young type 1 diabetic patients. METHODS: The Diabetes-Patienten-Verlaufsdaten is a longitudinal follow-up database, which collects data from 298 German and Austrian diabetes centres. Data available on diabetic patients aged <20 years were analysed statistically. RESULTS: We compared data for 159 Down's syndrome patients with diabetes and 41,983 type 1 diabetic patients. The former used less insulin, but showed better glycaemic control (HbA1c). Diabetes onset during the first 3 years of life occurred in 18.9% of Down's syndrome patients with diabetes and in 6.4% of type 1 diabetic patients. Antibody titres indicative of coeliac disease and thyroid peroxidase antibodies were more frequent in Down's syndrome patients with diabetes. No significant differences were found regarding the beta cell autoantibodies studied. CONCLUSIONS/INTERPRETATION: The age-of-onset distribution showed a shift towards younger ages and was bimodal in the Down's syndrome group. The better metabolic control found, despite intellectual impairment, in young Down's syndrome patients with diabetes cannot be conclusively explained by our data, but is likely to be due to a less complex lifestyle. Our data provide further confirmation that coeliac and thyroid antibodies are more prevalent in Down's syndrome. The presence of beta cell autoantibodies supports an autoimmune cause of diabetes in some children with Down's syndrome.

Intra-abdominal tuberculous peritonitis.

We report the case of a 15-year-old boy suffering from progressive dyspnea on exertion and painful abdominal protrusion. Final diagnosis of intra-abdominal tuberculosis (TB), including lymphadenopathy and abdominal abscess formation, was made following elective laparotomy. This type of disease is a rare manifestation of extrapulmonary tuberculosis. The imaging findings in unenhanced and contrast-enhanced MRI and laparoscopic images are presented. Differential diagnosis of abdominal abscess formation and other fungal or bacteriological infections, as well as the imaging findings of this type of lesion, are discussed. This case demonstrates that atypical manifestation of TB may remain unrecognized; thus, awareness of this kind of manifestation of tuberculosis may prevent patients from being subjected to inappropriate therapies.

[The detection of inflammation and the formation of HAMA following the administration of monoclonal antibody BW 250/183]. / Entzündungsnachweis und HAMA-Bildung nach Applikation des monoklonalen Antikörpers BW 250/183.

Experiences with the use of the 99mTc-labelled MAb BW 250/183 in the detection of inflammatory lesions are reported. In 160 of 354 investigated patients the results could be confirmed by other methods. The sensitivity (91%) and the specificity (82%) were very high for a diagnostic tool and were comparable with the results of other leukocyte scans as reported in the literature. The positive predictive value of the method was 93%. In 84 patients studied once and in 6 patients studied twice only one case of the latter group showed a positive HAMA response. It may be concluded that the detection of foci of inflammation with the 99mTc-labelled MAb BW 250/183 is of great diagnostic value and that its administration can be repeated without risk.