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Background A repeat biopsy is recommended, but often omitted in coeliac disease patients on a gluten-free diet. The effect of performing or not performing repeat biopsies is currently unknown. Aim To identify factors associated with and the significance of lacking biopsy for long-term outcome. Predictors and the importance of incomplete histological recovery after 1 year was investigated in re-biopsied patients. Methods A total of 760 patients participated in a nationwide follow-up study. Medical data were gathered via interviews and patient records, and blood samples were drawn for serology. Current symptoms and well-being were assessed by validated PGWB, SF-36 and GSRS questionnaires. Results Malabsorption was more common among those with a repeat biopsy (46%) than those without repeat biopsy (33%), P < 0.001, as were severe symptoms at diagnosis (24% vs. 16%, P = 0.05) and concomitant gastrointestinal (40% vs. 32%, P = 0.049) or musculoskeletal (35% vs. 27%, P = 0.023) diseases such as arthritis, osteoporosis and back pain. Repeat biopsy was more rare in subjects diagnosed in private care (11% vs. 23%, P < 0.001) or by screening (10% vs. 16%, P = 0.010). The groups were comparable as to current symptoms and dietary adherence, but those without re-biopsy were less confident of their diet (89% vs. 94%, P = 0.002) and more often seropositive on diet (14% vs. 9%, P = 0.012). They reported better SF-36 physical functioning ( P = 0.043) and less pain and indigestion ( P = 0.013 and P = 0.046 respectively) and total GSRS ( P = 0.052) score. Incomplete mucosal recovery was predicted by more advanced histological ( P < 0.001) and serological ( P = 0.001) disease at diagnosis, whereas the groups did not differ in long-term adherence, symptoms, seropositivity, questionnaire scores, frequency of fractures or malignancies. Conclusions Severe disease at diagnosis predicted the record of a repeat biopsy and incomplete mucosal recovery. Neither lacking biopsy nor incomplete recovery in a relative short time span of 1 year was associated with poorer long-term outcome, although survival bias cannot be excluded. [ABSTRACT FROM AUTHOR]

Background Refractory coeliac disease ( RCD) is thought to be a rare disorder, but the accurate prevalence is unknown. Aim We aimed to identify the prevalence of and the risk factors for developing RCD in a Finnish population where the clinical detection rate of coeliac disease is high. Methods The study involved 11 hospital districts in Finland where the number of treated RCD patients ( n = 44), clinically diagnosed coeliac disease patients ( n = 12 243) and adult inhabitants ( n = 1.7 million) was known. Clinical characteristics at diagnosis of coeliac disease between the RCD patients and patients with uncomplicated disease were compared. Results The prevalence of RCD was 0.31% among diagnosed coeliac disease patients and 0.002% in the general population. Of the enrolled 44 RCD patients, 68% had type I and 23% type II; in 9% the type was undetermined. Comparing 886 patients with uncomplicated coeliac disease with these 44 patients that developed RCD later in life, the latter were significantly older (median 56 vs 44 years, P < 0.001), more often males (41% vs. 24%, P = 0.012) and seronegative (30% vs. 5%, P < 0.001) at the diagnosis of coeliac disease. Patients with evolving RCD had more severe symptoms at the diagnosis of coeliac disease, including weight loss in 36% (vs. 16%, P = 0.001) and diarrhoea in 54% (vs. 38%, P = 0.050). Conclusions Refractory coeliac disease is very rare in the general population. Patients of male gender, older age, severe symptoms or seronegativity at the diagnosis of coeliac disease are at risk of future refractory coeliac disease and should be followed up carefully. [ABSTRACT FROM AUTHOR]

A response from the authors of the article "refractory coeliac disease - rigorous management revealing, or resulting in, rarity?" is presented.

In 2000-2004, we performed a focused search for individuals with Angelman syndrome (AS) and Prader-Willi syndrome (PWS) aiming to establish the prevalence data for the individuals born between 1984 and 2004 in Estonia. All persons with probable AS or PWS (n = 184) were studied using the DNA methylation test. Individuals with abnormal methylation were all further tested by chromosomal and FISH analysis, and if necessary for uniparental disomy and UBE3A gene mutation. Nineteen cases with abnormal methylation test result were identified. Seven of them had AS, including six (85.7%) due to 15q11-13 deletion and one paternal UPD15. Twelve subjects had PWS: 4 (33%) 15q11-13 deletions, 6 (50%) maternal UPD15, 1 unbalanced chromosome 14;15 translocation resulting in a chromosome 15pter-q13 deletion, and 1 Robertsonian 15q;15q translocation. The minimum livebirth prevalence in 1984-2004 for AS was 1:52,181 (95% CI 1:25,326-1:1,29,785) and for PWS 1:30,439 (95% CI 1:17,425-1:58,908). The livebirth prevalence of AS and PWS increased within this period, but the change was statistically significant only for PWS (P = 0.032), from expected 1:88,495 (95% CI 1:24,390-1:3,22,580) to expected 1:12,547 (95% CI 1:540-1:29,154). Six individuals with AS and 11 with PWS were alive on the prevalence day (January 1, 2005), indicating the point prevalence proportion of 1:56,112 (95% CI 1:25,780-1:1,52,899) and 1:30,606 (95% CI 1:17,105-1:61,311), respectively. Our results showing the birth prevalence of AS 1.7 times less than PWS challenge the opinion that both syndromes are equally represented, and are in line with the view that mutations in sperm and oocytes occur at different frequencies.

We report on a pure duplication of the proximal chromosome 2q in a 6.5-year-old boy with V-shaped midline cleft palate and bifid uvula, posteriorly located tongue, and micrognathia (Pierre Robin sequence), celiac disease, failure to thrive, and developmental delay. Cytogenetic and FISH analysis indicated a duplication of chromosome 2q13-q22. In general, pure proximal duplication or triplication of 2q is rare. The clinical features and chromosomal breakpoints of the 10 previously reported patients varied, and no common phenotype or proximal duplication/triplication 2q syndrome could be defined to date. However, based on four previous patients with different orofacial clefts and our case, a locus for orofacial clefting may be located at proximal 2q. The duplication/triplication comprised chromosome 2q13 in all five affected individuals including our patient. Our patient and three previous cases (two with cleft palate only (CPO) and one with cleft lip/palate (CL/P)) showed a cytogenetic breakpoint at 2q13, which could support the presence of a critical dominant gene disrupted by a common breakpoint, however, the fifth case with CPO showed different breakpoints, advocating against the disruption of a critical dominant gene and supporting that the overexpression of a gene(s) on chromosome 2q13-q21 may cause cleft palate only (CPO) and Pierre Robin sequence. Hence, our findings support either the presence of one locus for orofacial clefting (CL/P, CPO, and Pierre Robin sequence) between markers D2S1897 (chromosome 2q12.2) and D2S2023 (chromosome 2q14.2), or alternatively the presence of a locus for CPO and Pierre Robin sequence on chromosome 2q13-q21., ((c) 2005 Wiley-Liss, Inc.)

We report a newborn girl with intrachromosomal triplication of 3q25.3 --> q29 (mosaicism) who died at the age of 3.5 weeks due to her malformations. She demonstrated disproportionate short stature with short limbs, a prominent and hairy forehead, thick eyebrows, synophrys, small upturned nose, full cheeks, micrognathia, and low set malformed and posteriorly rotated ears, short and webbed neck, hydrocephalus, Dandy-Walker malformation, spina bifida, complex heart defect (ventricular and atrial septal defect, malrotation, and interrupted aortic arch), omphalocele, polycystic kidneys, postaxial polydactyly of left hand, and generalized hirsutism; all signs have been associated with the dup(3q) syndrome previously. The facial appearance (hairy forehead, thick eyebrows, synophrys, small upturned nose, full cheeks, micrognathia, low set malformed and posteriorly rotated ears) showed resemblance to the Brachmann-de Lange syndrome (BDLS), but the patient did not fulfill the diagnostic criteria for BDLS. There has been only one report of a direct triplication of chromosome 3 until now, but in our case the triplicated area is larger, located more proximally, and includes the hypothetical BDLS critical gene region-CDL1. Our findings lend support to distal chromosome 3q, or chromosome 3q26.3, comprises the critical area for the dup(3q) phenotype resembling the BDLS., (2005 Wiley-Liss, Inc.)

It is well documented that distal 9p monosomy can be associated with XY sex reversal. Recently, the possibility of DMRT1 and/or DMRT2 (the genes for doublesex and mab-3 related transcription factor 1 and 2) being the sex determining genes(s) at 9p has been raised. DMRT1 and DMRT2 map near the 9p telomere, distal of marker D9S1779. We describe here three unrelated females with distal 9p monosomy, one with XY complement and two with XX complements. In each individual, fluorescent in situ hybridization predicted the loss of the DMRT genes. Patient 1, an XY individual with monosomy 9pter --> p24.1 approximately 24.2 and trisomy 7q32 --> qter had normal female external genitalia, a blind ending vagina, no uterus, a Fallopian tube on the right, and bilateral ovotestes with primitive ovarian tissue. She also had extreme growth retardation. Around 80 cases of distal 9p monosomy have been reported previously, but there has been no report of ovotestes or gonads comprising ovarian tissue in a XY patient with 9p deletion. Findings in Patient 1 suggest that the phenotypic spectrum of the heterozygous DMRT deletion may include true hermaphroditism. Patients 2 and 3 were 12- and 14-year-old females with XX complements, normal external genitalia, and normal pubertal development. Patient 2 had pure monosomy 9pter --> p23 and Patient 3 had monosomy 9pter --> p22.3 approximately 23 combined with trisomy 3pter --> p23 approximately 24. To date, detailed reports on the gonadal status of XX 9p-females have been limited to prepubertal girls. Patients 2 and 3 are the first females reported to have distal 9p monosomy and a normal puberty., ((c) 2004 Wiley-Liss, Inc.)