Who’s Who in Research?

Harry Angelman b.13 August 1915 d.8 August 1996
MB ChB Liverpool (1938) DCH (1940) MRCP (1947) MD (1948) FRCP (1971)

Harry Angelman was a paediatrician who named and identified the congenital condition known as ‘Angelman Ssyndrome’ which has since been named after him. He was born in Birkenhead, the fifth of six children of Samuel and Elizabeth Angelman. His multi-lingual father put great emphasis on studying. Harry was educated at the Birkenhead Institute and at Liverpool University, qualifying in 1938. Poor health in children, endemic in industrial towns of the 1930s, made an indelible impression on Harry. He decided to specialize in paediatrics, gained his diploma in child health and took up a post at Booth Hall Children’s Hospital, Manchester. Harry then went to Queen Mary’s Children’s Hospital, Carshalton, where hundreds of children, many suffering from tuberculosis or rheumatic heart disease, were housed in bungalows. More children came from London as the blitz intensified. The hospital was bombed several times, but they never lost a child.

After demobilization his first appointment was in adult medicine at St Mary Abbott’s Hospital, London. Dr Angelman then went on to work as a senior registrar at the Royal Liverpool Children’s Hospital.

In 1950 he was appointed consultant paediatrician to the Warrington Group of Hospitals. Here he raised the standard of the paediatric ward from a few cots with an open fire, until it was featured in a national nursing magazine.

It was at Warrington that the story of Angelman Syndrome began and it is best told in Harry’s own words, written in 1991: "It was purely by chance that nearly thirty years ago three handicapped children were admitted at various times to my children’s ward. They had a variety of disabilities and, although at first sight they seemed to be suffering from different conditions, I felt that there was a common cause for their illness. The diagnosis was purely a clinical one because in spite of technical investigations which today are more refined, I was unable to establish scientific proof that the three children all had the same handicap. In view of this, I hesitated to write about them in the medical journals. However, when on holiday in Italy, I happened to see an oil painting in the Castelvecchio museum in Verona called 'A boy with a puppet’. The boy’s laughing face and the fact that my patients exhibited jerky movements gave me the idea of writing an article about the three children with the title of ‘puppet children’. It was not a name that pleased all parents but it served as a means of combining the three little patients into a single group. Later the name was changed to Angelman Syndrome. This article was published in 1965 (Develop. Med. Child. Neurol., 7:681-688) and, after some initial interest, lay almost forgotten until the early eighties. In fact many doctors denied that such a condition existed. In the past ten years American and English doctors have placed the syndrome on a firm footing with the ability to establish the diagnosis beyond doubt."

In 1986 the Angelman Syndrome Support Group was formed in Waterlooville, Hampshire, to offer a nationwide network of support for affected families. The ASSG disbanded and the Angelman Syndrome Support Education and Research Trust (ASSERT) formed in its place. ASSERT was renamed AngelmanUK in 2018.

Dr Angelman died in Gosport War Memorial Hospital, Portsmouth. The last letter Harry received was a gracious appreciation of his work from President Clinton who congratulated him on his "remarkable accomplishments".

This letter is in the possession of AngelmanUK and the hospital now features a plaque commemorating Dr Angelman’s work. AngelmanUK is also very honoured to be in regular contact with several members of Dr & Mrs Angelman’s family.

I first became interested in Angelman Syndrome as a junior doctor, shortly after I had started training in Clinical Genetics. Whilst working at the Institute of Child Health in London Professor Marcus Pembrey introduced me to a family who had three daughters with Angelman Syndrome, and told me about a number of other families known to Great Ormond Street Hospital. This resonated with me as I remember being shown a photograph of this same family when they were published in the literature whilst I was a student in Manchester. The genetic basis of Angelman Syndrome had just started to be identified, as a couple of patients had been suggested to have deletions on chromosome 15 , interestingly in labs in Manchester and London. Marcus suggested that I might want to do a research study on Angelman Syndrome and encouraged me to apply for an Action Research Training Fellowship which I was subsequently awarded after interview. Thus began a career-long interest in Angelman Syndrome.

During the next three years I travelled around the UK recruiting patients to my study and met some amazing Angelman individuals and their families. I also undertook laboratory work under the supervision of Prof Sue Malcolm and we described the first Angelman patients with uniparental disomy of chromosome 15. I had the chance to travel to the first Angelman Syndrome Foundation meeting in the USA which was in Florida. There I met Dr Harry Angelman and his wife Audrey and kept in touch with them over the years until they passed away.

In 1992 I moved back up to Manchester and completed my MD thesis on a Clinical and Genetic Study of Angelman Syndrome. When the UBE3A gene was discovered several years later I worked with our Manchester laboratory to set up a diagnostic service for Angelman Syndrome in the UK and continued to see many patients in clinic. I have also been involved in drawing up the consensus diagnostic criteria for Angelman Syndrome, the development of management guidelines for Angelman Syndrome and guidelines for genetic testing. For several years I have worked to identify the cause of symptoms in individuals with AS-like disorders where we could not identify chromosome 15 abnormalities and this has become one of my specific research areas. As a member of the European Reference Network ERN ITHACA I am able to share ideas and collaborate with a number of other specialists in AS throughout the EU.

Together with Dr Dan Hindley and a multidisciplinary team we now run a specialist clinic for Angelman Syndrome from the Manchester Centre For Genomic Medicine and continue to be involved in clinical research in this area. I have had a relationship with Angelman Syndrome support groups spanning nearly thirty years and hope to continue to be involved for several years to come.

Stormy Chamberlain has a PhD in Molecular Genetics from the University of Florida. She is an Associate Professor in Genetics and Genome Science.
Her laboratory uses induced pluripotent stem cells to model and study human imprinting disorders (Angelman Syndrome, Prader-Willi Syndrome and Duplication 15q Syndrome).

Ype Elgersma is a Professor of Molecular Neuroscience at Erasmus Medical Centre in Rotterdam and is also the Scientific Director of ENCORE Expertise Centre for Neurodevelopmental Disorders. His current focus is trying to understand how motor deficits in Angelman Syndrome arise, and whether the neurological deficits are reversible.

The Zylka lab studies genetic and environmental risks for autism. In addition, they study molecular and brain mechanisms that underlie pain sensation. Their long-term goal is to uncover new treatments for chronic pain and neurodevelopmental disorders, like autism, Rett syndrome and Angelman syndrome.
In collaboration with Drs. Ben Philpot and Bryan Roth, they found that topoisomerase inhibitors unsilence a dormant but functional copy of Ube3a in mice. They aim to advance our understanding of how these drugs work, with the ultimate goal of developing treatments for Angelman Syndrome.

Chris Oliver is Professor of Neurodevelopmental Disorders at the University of Birmingham and director of the Cerebra Centre for Neurodevelopmental Disorders. He trained as a clinical psychologist at Edinburgh University before completing a PhD on self-injurious behaviour in people with intellectual disability at the Institute of Psychiatry, London. Chris is currently researching early intervention, behaviour disorders in people with severe intellectual disability and autism spectrum disorder, behavioural phenotypes in genetic syndromes and neuropsychological and behavioural assessment for people with severe intellectual disability. He has published over 170 peer reviewed articles in scientific journals (including over 20 papers on Angelman Syndrome), is Editor in Chief for the Journal of Intellectual Disability Research and serves on a number of scientific advisory committees for syndrome support groups. Sadly, he supports Luton Town Football Club.

http://www.findresources.co.uk/the-syndromes/angelman