Angelman syndrome (AS) is characterised by severe developmental delay or intellectual disability, severe speech impairment, gait ataxia and a unique behaviour with an overly happy demeanour that includes frequent laughing, smiling, and excitability. Developmental delays are first noted at around age six months; however, the clinical features of AS do not become apparent until after age one year. Angelman syndrome has multiple causes, all affecting chromosome region 15q11.1-q11.3.

Charcot-Marie-Tooth neuropathy type 1 (CMT1) is a demyelinating peripheral neuropathy characterised by distal muscle weakness and atrophy and sensory loss. It is usually slowly progressive and often associated with pes cavus foot deformity and bilateral foot drop. Affected individuals usually become symptomatic between age five and 25 years.

Chromosomal breakage syndromes are a group of genetic disorders that are characterised by a defect in DNA repair mechanisms or genomic instability, and patients with these disorders show increased predisposition to cancer in addition to distinct clinical presentations. VCGS offers testing for Ataxia talengiectasia and Bloom syndrome.

Cystic fibrosis (CF) is an inherited condition affecting breathing and digestion. CF causes the build-up of thick mucus which traps bacteria, resulting in recurrent infections that damage the lungs. Thick mucus in the gut also makes digestion of food difficult. People with CF require daily physiotherapy to clear mucus from their lungs, frequent courses of antibiotics and need to take medicine to help with digestion. There is no cure for CF but better treatments are under research and development.

Dentatorubral-pallidoluysian atrophy (DRPLA) is a progressive disorder of ataxia, myoclonus, epilepsy, and progressive intellectual deterioration in children and ataxia, choreoathetosis, and dementia or character changes in adults. Age of onset varies from childhood through to late adulthood

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are types of neuromuscular disorders that affect the nerves and the muscles.

Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability. People with FXS can have developmental delay, learning difficulties, anxiety, autism and epilepsy. The features of FXS vary from mild to severe with males more likely to be severely affected than females because the gene is found on the X-chromosome.

Friedreich ataxia (FRDA) is characterised by slowly progressive ataxia which becomes apparent between age ten and 15 years. FRDA is typically associated with muscle weakness which impacts on speach, heart function, spasticity in the lower limbs and scoliosis, Approximately one third of individuals with FRDA will also develop diabetes mellitus.

Nonsyndromic hearing loss is a partial or total loss of hearing that is not associated with other signs and symptoms. Nonsyndromic hearing loss can be caused by alterations in over 90 genes however the most commonly associated genes are GJB2 and GJB6 genes. The GJB2 and GJB6 genes provides instructions for making the connexin 26 and connexin 30 proteins respectively. Alterations in the GJB2 or GJB6 gene change their connexin proteins, which may affect the function or survival of cells that are needed for hearing.

Genetics and Genomics

Huntington disease is a progressive brain disorder that causes uncontrolled movements, emotional problems, and loss of thinking ability (cognition).

Emery-Dreifuss muscular dystrophy is a condition that chiefly affects muscles used for movement (skeletal muscles) and heart (cardiac) muscle. Most affected individuals experience joint deformities called contractures, slowly progressive muscle weakness and wasting, beginning in muscles of the upper arms and lower legs and progressing to muscles in the shoulders and hips. Mutations in the Emerin (EMD) and Lamin (LMNA) genes cause of X-linked and autosomal dominant Emery-Dreifuss muscular dystrophy.

This MLPA assay for analysis of the OTOA, STRC, CATSPER2 genes accounts for the majority of SNHL associated copy number changes and is suitable as a second tier test following a negative result from GJB2/GJB6 (Connexin 26/30) testing.

Myotonic dystrophy type 1 (DM1) is a multisystem disorder that affects skeletal and smooth muscle as well as the eye, heart, endocrine system and central nervous system. Myotonic dystrophy has three categories: mild, classic, and congenital. Congenital DM1 is the severist form of DM1 and is characterised by hypotonia and severe generalised weakness at birth, often with respiratory insufficiency; intellectual disability is common. DM1 is caused by the alteration of the DMPK gene.

Prader-Willi syndrome (PWS) is characterised by severe hypotonia and feeding difficulties in early infancy, followed in later infancy or early childhood by excessive eating and gradual development of morbid obesity (unless eating is externally controlled). All individuals have some degree of cognitive impairment. Prader-willi has multiple causes, all affecting chromosome region 15q11.1-q11.3.

SMA is an autosomal recessive condition that affects nerves in the spinal cord and causes muscles to get progressively weaker. There are four types of SMA with SMA type 1 being the most common and most severe. Babies with SMA type 1 have weak muscles from birth and usually do not live past two years of age. SMA types 2 and 3 are less severe than type 1 and symptoms typically develop in childhood. SMA type 4 is the mildest form and develops during adulthood. There is no cure for SMA, however treatment is aimed at managing symptoms and improving quality of life.

Spinocerebellar ataxia (SCA) is a progressive, degenerative, genetic disease with multiple types, each of which could be considered a disease in its own right.

Stickler syndrome is a group of hereditary conditions characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and joint problems.

We all have 23 pairs of chromosomes with one chromosome of each pair coming from each parent. Uni-parental disomy (UPD) occurs when both copies of the one chromosome come from one parent. For most chromosomes this does not affect how we develop, but a for a small group of chromosomes this can result in a group of unrelated conditions called imprinting disorders. UPD of chromosomes 6,7,11,14 and 15 are known to be associated with genetic conditions.