Clinical Genetics and Genomics

• Introduction


• Adoption


• Approach to the consultation with a child with dysmorphism, congenital malformation or developmental delay


• Autosomal dominant (AD) inheritance


• Autosomal recessive (AR) inheritance


• Communication skills


• Complex inheritance


• Confidentiality


• Confirmation of diagnosis


• Consent for genetic testing


• Genetic basis of cancer


• Genetic code and mutations


• Genomes and genomic variation


• Genomic imprinting


• Genomic sequencing and interpretation of data from WES or WGS analyses


• Mitochondrial inheritance


• Reproductive options


• Testing for genetic status


• Timing and origin of new dominant mutations


• Useful resources


• X-linked dominant (XLD), semi-dominant, pseudoautosomal and male sparing inheritance


• X-linked recessive inheritance


• Clinical Approach


• Ambiguous genitalia (including sex reversal)


• Anal anomalies (atresia, stenosis)


• Anterior segment eye malformations


• Arthrogryposis


• Ataxic adult


• Ataxic child


• Brachydactyly


• Broad thumbs


• Cardiomyopathy in children under 10 years


• Cataract


• Cerebellar anomalies


• Cerebral palsy


• Chondrodysplasia punctata


• Cleft lip and palate


• Coarse facial features


• Coloboma


• Congenital heart disease


• Congenital hypothyroidism


• Corneal clouding


• Deafness in early childhood


• Developmental delay in the child with consanguineous parents


• Developmental regression


• Duane retraction syndrome


• Dysmorphic child


• Dystonia


• Ear anomalies

Dr Helen Firth, DM FRCP DCH is a Consultant Clinical Geneticist at Cambridge University Hospitals, an Honorary Faculty Member of the Wellcome Trust Sanger Institute, and a Bye-Fellow of Newnham College, Cambridge. Her main research interests are in mapping the clinical genome and the matching of rare genomic variants to empower discovery and diagnosis in rare disease.

In 2004, she initiated the DECIPHER project (http://decipher.sanger.ac.uk) that enables clinicians and scientists around the world to share information about rare genomic variants to facilitate diagnosis and help to elucidate the role of genes whose function is not yet known. In 2010 Dr Firth became Clinical Lead for the Deciphering Developmental Disorders study (DDD study) (http://www.ddduk.org), one of the world's largest nationwide, genome-wide sequencing projects in rare disease. The study aims to improve diagnosis and further understanding of the genomic architecture of severe developmental disorders.

Dr Jane Hurst is a clinician working full time as a clinical geneticist in the one of the leading children's hospitals in the world; a centre of excellence for the diagnosis and treatment of rare diseases. She moved to her current post in 2010 to lead the dysmorphology service after 18 years working in Oxford, UK.

Although primarily a patient-focussed clinician, she has always worked closely with scientific colleagues by identifying families that give important clues to the genetic aetiology. Thus early in her career she identified the first family shown to have leptin deficiency and the two families that led to the cloning of the FOXP2 gene.

Review from previous edition:
It is very refreshing to review a book written for clinicians by clinicians, which is in a format that reflects situations actually encountered in practice. Information provided by the referring doctor to a clinical geneticist or other specialist before a clinic or ward consultation is usually limited. This new text takes common referral indications and, in a standardized format that manages to be brief and clear without skimping on detail, reminds the clinician of diagnostic possibilities and strategies for investigation and management. This will allow the best possible use to be made of an individual consultation by both the patient and the doctor. Dian Donnai, Professor of Medical Genetics, University of Manchester, Consultant Clinical Geneticist, Regional Genetics Service, St Mary's Hospital, Manchester, UK