Journal of Medical Genetics 

About: Journal of Medical Genetics is an academic journal published by BMJ. The journal publishes majorly in the area(s): Population & Karyotype. It has an ISSN identifier of 0022-2593. Over the lifetime, 9456 publications have been published receiving 413698 citations. The journal is also known as: J Med Genet & J. Med. Genet,.

Genetic heterogeneity in osteogenesis imperfecta.

Abstract: An epidemiological and genetical study of osteogenesis imperfecta (OI) in Victoria, Australia confirmed that there are at least four distinct syndromes at present called OI. The largest group of patients showed autosomal dominant inheritance of osteoporosis leading to fractures and distinctly blue sclerae. A large proportion of adults had presenile deafness or a family history of presenile conductive hearing loss. A second group, who comprised the majority of newborns with neonatal fractures, all died before or soon after birth. These had characteristic broad, crumpled femora and beaded ribs in skeletal x-rays. Autosomal recessive inheritance was likely for some, if not all, of these cases. A third group, two thirds of whom had fractures at birth, showed severe progressive deformity of limbs and spine. The density of scleral blueness appeared less than that seen in the first group of patients and approximated that seen in normal children and adults. Moreover, the blueness appeared to decrease with age. All patients in this group were sporadic cases. The mode of inheritance was not resolved by the study, but it is likely that the group is heterogeneous with both dominant and recessive genotypes responsible for the syndrome. The fourth group of patients showed dominant inheritance of osteoporosis leading to fractures, with variable deformity of long bones, but normal sclerae.

The revised Ghent nosology for the Marfan syndrome

Abstract: The diagnosis of Marfan syndrome (MFS) relies on defined clinical criteria (Ghent nosology), outlined by international expert opinion to facilitate accurate recognition of this genetic aneurysm syndrome and to improve patient management and counselling. These Ghent criteria, comprising a set of major and minor manifestations in different body systems, have proven to work well since with improving molecular techniques, confirmation of the diagnosis is possible in over 95% of patients. However, concerns with the current nosology are that some of the diagnostic criteria have not been sufficiently validated, are not applicable in children or necessitate expensive and specialised investigations. The recognition of variable clinical expression and the recently extended differential diagnosis further confound accurate diagnostic decision making. Moreover, the diagnosis of MFS—whether or not established correctly—can be stigmatising, hamper career aspirations, restrict life insurance opportunities, and cause psychosocial burden. An international expert panel has established a revised Ghent nosology, which puts more weight on the cardiovascular manifestations and in which aortic root aneurysm and ectopia lentis are the cardinal clinical features. In the absence of any family history, the presence of these two manifestations is sufficient for the unequivocal diagnosis of MFS. In absence of either of these two, the presence of a bonafide FBN1 mutation or a combination of systemic manifestations is required. For the latter a new scoring system has been designed. In this revised nosology, FBN1 testing, although not mandatory, has greater weight in the diagnostic assessment. Special considerations are given to the diagnosis of MFS in children and alternative diagnoses in adults. We anticipate that these new guidelines may delay a definitive diagnosis of MFS but will decrease the risk of premature or misdiagnosis and facilitate worldwide discussion of risk and follow-up/management guidelines.

Hirschsprung disease, associated syndromes and genetics: a review

Abstract: Hirschsprung disease (HSCR, aganglionic megacolon) represents the main genetic cause of functional intestinal obstruction with an incidence of 1/5000 live births. This developmental disorder is a neurocristopathy and is characterised by the absence of the enteric ganglia along a variable length of the intestine. In the last decades, the development of surgical approaches has importantly decreased mortality and morbidity which allowed the emergence of familial cases. Isolated HSCR appears to be a non-Mendelian malformation with low, sex-dependent penetrance, and variable expression according to the length of the aganglionic segment. While all Mendelian modes of inheritance have been described in syndromic HSCR, isolated HSCR stands as a model for genetic disorders with complex patterns of inheritance. The tyrosine kinase receptor RET is the major gene with both rare coding sequence mutations and/or a frequent variant located in an enhancer element predisposing to the disease. Hitherto, 10 genes and five loci have been found to be involved in HSCR development.

Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study.

Abstract: We present clinical data on 558 patients with deletions within the DiGeorge syndrome critical region of chromosome 22q11. Twenty-eight percent of the cases where parents had been tested had inherited deletions, with a marked excess of maternally inherited deletions (maternal 61, paternal 18). Eight percent of the patients had died, over half of these within a month of birth and the majority within 6 months. All but one of the deaths were the result of congenital heart disease. Clinically significant immunological problems were very uncommon. Nine percent of patients had cleft palate and 32% had velopharyngeal insufficiency, 60% of patients were hypocalcaemic, 75% of patients had cardiac problems, and 36% of patients who had abdominal ultrasound had a renal abnormality. Sixty-two percent of surviving patients were developmentally normal or had only mild learning problems. The majority of patients were constitutionally small, with 36% of patients below the 3rd centile for either height or weight parameters.

Malignant peripheral nerve sheath tumours in neurofibromatosis 1

Abstract: Background: Cross sectional studies have shown that 1-2% of patients with neurofibromatosis 1 (NF1) develop malignant peripheral nerve sheath tumours (MPNST). However, no population based longitudinal studies have assessed lifetime risk. Methods: NF1 patients with MPNST were ascertained from two sources for our north west England population of 4.1 million in the 13 year period 1984-1996: the North West Regional NF1 Register and review of notes of patients with MPNST in the North West Regional Cancer Registry. Results: Twenty-one NF1 patients developed MPNST, equivalent to an annual incidence of 1.6 per 1000 and a lifetime risk of 8-13%. There were 37 patients with sporadic MPNST. The median age at diagnosis of MPNST in NF1 patients was 26 years, compared to 62 years in patients with sporadic MPNST (p Conclusion: The lifetime risk of MPNST in NF1 is much higher than previously estimated and warrants careful surveillance and a low threshold for investigation.