A new locus for Seckel syndrome on chromosome 18p11.31-q11.2

Seckel syndrome (MIM 210600) is a rare autosomal recessive disorder with a heterogeneous appearance. Key features are growth retardation, microcephaly with mental retardation, and a characteristic 'bird-headed' facial appearance. We have performed a genome-wide linkage scan in a consanguineous family of Iraqi descent. By homozygosity mapping a new locus for the syndrome was assigned to a approximately 30 cM interval between markers D18S78 and D18S866 with a maximum multipoint lod score of 3.1, corresponding to a trans-centromeric region on chromosome 18p11.31-q11.2. This second locus for Seckel syndrome demonstrates genetic heterogeneity and brings us a step further towards molecular genetic delineation of this heterogeneous condition

Pycnodysostosis--common ancestor of some Danish patients. Examination and diagnosis based on molecular genetics

Eight patients with pycnodysostosis from six Danish families were examined for mutations in the cathepsin K gene. Three different mutations are the cause of pycnodysostosis in the six families--five of whom come from Ringkøbing County and one from Vejle County. One mutation has a high frequency in the families from Ringkoebing County. The five families are related through a common ancestor, who introduced the mutation around the year 1100. The disease is described with respect to aetiology, symptoms, prognosis, diagnosis, and symptomatic treatment. Research in pycnodysostosis may bring important knowledge to the understanding of related diseases, such as osteoporosis

Constipation in adults with neurofibromatosis type 1

Abstract Background Neurofibromatosis type 1 (NF1) is an autosomal-dominant disease characterised by symptoms of the skin, eyes, nervous system and bones. A previous study indicated that constipation, large rectal diameters and prolonged colorectal transit times are common in children with NF1. The aim of the present study was to investigate and compare the prevalence of gastrointestinal symptoms in adult patients with NF1 to their unaffected relatives serving as the control group. Patients with NF1 were recruited from one of two Danish National Centres of Expertise for NF1 and their unaffected relatives were invited to participate as controls. Gastrointestinal symptoms were assessed with a web-based, self-administered, validated, Rome® III diagnostic questionnaire. Logistic regression was used to estimate the prevalence of functional dyspepsia, IBS and functional constipation in each group and the groups were compared using their odds ratios. Results The response rates for patients and controls were 66.4% and 82.4%, respectively. We compared 175 patients, median age 34.2 (IQR = 20.1) and 91 of their unaffected relatives, median age 42.0 (IQR = 12). The overall likelihood of fulfilling the diagnostic criteria for functional constipation, irritable bowel syndrome or functional dyspepsia was 33.1% among patients vs. 14.3% among controls, (odds ratio (OR): 2.97; 95% CI: 1.56–5.66) and after adjustment for age and gender (OR: 3.06; 95% CI: 1.62–5.79). The likelihood of functional constipation was higher among patients (OR: 3.80; 95% CI: 1.27–11.31), and this was still true after adjustment (OR: 3.49; 95% CI: 1.14–10.64). The likelihood of irritable bowel syndrome (OR: 2.29; 95% CI: 0.98–5.33) was evident after adjustment (OR: 2.46; 95% CI: 1.10–5.47), whereas there was no difference in the likelihood of functional dyspepsia (OR: 2.35; 95% CI: 0.67–8.32) after adjustment (OR:2.25; 95% CI: 0.70–7.17). Conclusions Overall, having symptoms usually attributed to either functional dyspepsia, IBS or functional constipation is more common in adults with NF1 compared to unaffected relatives. Of the three, the likelihood of constipation is markedly higher. The high prevalence of constipation indicates that it is not functional but part of the NF1 disorder