PRACTICAL GENETICS SERIES – New to European Journal of Human Genetics!

The new, monthly Practical Genetics series delivers a one–stop–shop information resource for genetics clinicians.
Read the following papers in the series FREE online to find out more.

Articles

Nephronophthisis FREE
Roslyn J Simms, Lorraine Eley and John A Sayer

Nephronophthisis (NPHP) is an autosomal recessive kidney disorder characterized by chronic tubulointerstitial nephritis and leading to end-stage renal failure. NPHP as a renal entity is often part of a multisystem disorder and has been associated with many syndromes including Joubert syndrome (and related disorders) and Senior-Loken syndrome. [Continues ...]

Treacher Collins syndrome: etiology, pathogenesis and prevention FREE
Paul A Trainor, Jill Dixon and Michael J Dixon

Treacher Collins syndrome (TCS) is a rare congenital disorder of craniofacial development that arises as the result of mutations in the TCOF1 gene, which encodes a nucleolar phosphoprotein known as Treacle. Individuals diagnosed with TCS frequently undergo multiple reconstructive surgeries, which are rarely fully corrective. [Continues ...]

Kallmann syndrome FREE
Catherine Dodé and Jean-Pierre Hardelin

The Kallmann syndrome (KS) combines hypogonadotropic hypogonadism (HH) with anosmia. This is a clinically and genetically heterogeneous disease. KAL1, encoding the extracellular glycoprotein anosmin-1, is responsible for the X chromosome-linked recessive form of the disease. [Continues ...]

Prader—Willi syndrome FREE
Suzanne B Cassidy and Daniel J Driscoll

Prader—Willi syndrome (PWS) is a highly variable genetic disorder affecting multiple body systems whose most consistent major manifestations include hypotonia with poor suck and poor weight gain in infancy; mild mental retardation, hypogonadism, growth hormone insufficiency causing short stature for the family, early childhood-onset hyperphagia and obesity, characteristic appearance, and behavioral and sometimes psychiatric disturbance. [Continues ...]

Fragile X syndrome FREE
Kathryn B Garber, Jeannie Visootsak and Stephen T Warren

Fragile X syndrome, an X-linked dominant disorder with reduced penetrance, is associated with intellectual and emotional disabilities ranging from learning problems to mental retardation, and mood instability to autism. It is most often caused by the transcriptional silencing of the FMR1 gene, due to an expansion of a CGG repeat found in the 5'-untranslated region. [Continues ...]

Smith–Lemli–Opitz syndrome: pathogenesis, diagnosis and management FREE
Forbes D Porter

Smith–Lemli–Opitz syndrome (SLOS) is a malformation syndrome due to a deficiency of 7-dehydrocholesterol reductase (DHCR7). DHCR7 primarily catalyzes the reduction of 7-dehydrocholesterol (7DHC) to cholesterol. In SLOS, this results in decreased cholesterol and increased 7DHC levels, both during embryonic development and after birth. [Continues ...]

Smith–Magenis syndrome FREE
Sarah H Elsea and Santhosh Girirajan

Smith–Magenis syndrome (SMS) is a complex neurobehavioral disorder caused by haploinsufficiency of the retinoic acid-induced 1 (RAI1) gene on chromosome 17p11.2. Diagnostic strategies include molecular identification of a 17p11.2 microdeletion encompassing RAI1 or a mutation in RAI1. G-banding and fluorescent in situ hybridization (FISH) are the classical methods used to detect the SMS deletions, while multiplex ligation-dependent probe amplification (MLPA) and real-time quantitative PCR are the newer, cost-effective, and high-throughput technologies. [Continues ...]

Alström Syndrome FREE
Jan D Marshall, Sebastian Beck, Pietro Maffei and Jürgen K Naggert

Alström Syndrome is an autosomal recessive, single gene disorder caused by mutations in ALMS1 (Chr 2p13), a novel gene of currently unknown molecular function. Alström Syndrome is multisystemic, with cone-rod retinal dystrophy leading to juvenile blindness, sensorineural hearing loss, obesity, insulin resistance with hyperinsulinemia, and type 2 diabetes mellitus. [Continues ...]

Marfan syndrome: clinical diagnosis and management FREE
John C S Dean

Marfan syndrome is a multisystem connective tissue disorder usually associated with mutation in fibrillin, and occasionally with mutation in TGFBR1 or 2. The clinical diagnosis is made using the Ghent nosology, which will unequivocally diagnose or exclude Marfan syndrome in 86% of cases. Use of a care pathway can help implementation of the nosology in the clinic. The penetrance of some features is age dependent, so the nosology must be used with caution in children. [Continues ...]

Joubert syndrome (and related disorders) (OMIM 213300) FREE
Melissa A Parisi, Dan Doherty, Phillip F Chance and Ian A Glass

Joubert syndrome (JS) and related disorders are characterized by the 'molar tooth sign' (cerebellar vermis hypoplasia and brainstem anomalies) on MRI, hypotonia, developmental delay, ataxia, irregular breathing pattern and abnormal eye movements. [Continues ...]

CHARGE syndrome: an update FREE
Damien Sanlaville and Alain Verloes

CHARGE syndrome is a rare, usually sporadic autosomal dominant disorder due in 2/3 of cases to mutations within the CHD7 gene. The clinical definition has evolved with time. The 3C triad (Coloboma-Choanal atresia-abnormal semicircular Canals), arhinencephaly and rhombencephalic dysfunctions are now considered the most important and constant clues to the diagnosis. [Continues ...]

Sotos syndrome FREE
Katrina Tatton-Brown and Nazneen Rahman

Sotos syndrome is an autosomal dominant condition characterised by a distinctive facial appearance, learning disability and overgrowth resulting in tall stature and macrocephaly. In 2002, Sotos syndrome was shown to be caused by mutations and deletions of NSD1, which encodes a histone methyltransferase implicated in chromatin regulation. [Continues ...]

Neurofibromatosis 1 FREE
Rosalie E Ferner

Neurofibromatosis 1 predisposes affected individuals to the development of benign and malignant tumours that are frequently disfiguring and difficult to manage. However, advances in molecular biology and the development of mouse models have facilitated our understanding of disease pathogenesis. [Continues ...]

Otopalatodigital syndrome spectrum disorders: otopalatodigital syndrome types 1 and 2, frontometaphyseal dysplasia and Melnick–Needles syndrome FREE
Stephen P Robertson

The term otopalatodigital syndrome spectrum disorders is an umbrella category that includes four phenotypically related conditions, otopalatodigital syndrome types 1 and 2, frontometaphyseal dysplasia and Melnick–Needles syndrome. The phenotype of these conditions in the male ranges from a severe perinatally lethal multiple malformation syndrome to a mild skeletal dysplasia. [Continues ...]

The Börjeson–Forssman–Lehman syndrome (BFLS, MIM #301900) FREE
Jozef Gécz , Gillian Turner, John Nelson & Michael Partington

Börjeson–Forssman–Lehman syndrome was first described in 1962. Many similar families and isolated cases have been reported since. In nineteen of them, including the original family, the clinical diagnosis was confirmed by the identification of a mutation in the responsible gene, PHF6. Summarizing recent clinical and molecular studies of this X–chromosome linked mental retardation syndrome we aim to offer a useful resource for its identification among the affected male and female subjects. [Continues ...]

The challenges of Proteus syndrome: diagnosis and management FREE
Leslie Biesecker

Proteus syndrome (PS) is a disorder of patchy or mosaic postnatal overgrowth of unknown etiology. The onset of overgrowth typically occurs in infancy and can involve any tissue of the body. Commonly involved tissues include connective tissue and bone, skin, central nervous system, the eye, but it apparently can affect any tissue. Diagnosing of PS is difficult and the diagnostic criteria are controversial. [Continues ...]

Tuberous sclerosis FREE
John R W Yates

Tuberous sclerosis is a serious inherited disease which poses major challenges for affected families and those caring for them. Identification of the genes causing the condition and study of their protein products has shed light on the pathogenesis of the disease and provided valuable new information about signalling pathways regulating protein synthesis and cell growth. There is now the exciting possibility of drug therapy for some of the manifestations of the disease. [Continues ...]

Rubinstein–Taybi syndrome FREE
Raoul C M Hennekam

In this review a short overview of pertinent clinical and molecular data of the Rubinstein–Taybi syndrome are provided. A diagnostic decision algorithm, and major issues that should be considered in the management of patients are discussed. Suggestions for further research are given. [Continues ...]

Editorial

Practical genetics series introduction: Information overload, a double–edged sword FREE
Philip L Beales

Rett syndrome: new clinical and molecular insights FREE
Sarah L Williamson and John Christodoulou

In this review, we give a clinical overview of Rett syndrome (RTT), and provide a framework for clinical and molecular approaches to the diagnosis of this severe neurodevelopmental disorder. We also discuss issues that need to be considered in the management of RTT patients, and raise some of the challenges associated with genetic counselling. [Continues ...]

Practical Genetics series is updated monthly - check this site regularly for updates.

Published in association with Orphanet