22q11.2 deletion syndrome and a participatory approach to research

Those holding governmental purse strings must be persuaded to understand that rare disorders are relatively common

That’s it! That’s it! That explains what we have been seeing in Philadelphia,” is how paediatric endocrinologist Dr Angelo DiGeorge (1921–2009) responded after Dr Max Cooper addressed the US Society for Paediatric Research in 1965. Cooper reported experimental evidence – from chickens – indicating “that the lymphoid system is composed of two distinct cell populations, each with a separate embryological origin and different morphological and functional characteristics”, writes Ned Stafford in DiGeorge’s obituary (BMJ, 2009; 339: b5379).

Notwithstanding a dissenting audience member who advised that chickens are not humans, DiGeorge recognised that Cooper’s observations explained the absence of cellular immunity despite the presence of antibody-producing cells in three athymic children whom DiGeorge had attended at Philadelphia’s St Christopher’s Hospital. In 1967, ‘Lymphocytes in Congenital Absence of the Thymus’ was published in Nature (1967, 214: 580-582), heralding the introduction of DiGeorge syndrome to the medical lexicon.

Also known as chromosome 22q11.2 deletion syndrome (22q11.2DS) this genetic condition includes clinical features like hypoparathyroidism and hypocalcaemia, thymic hypoplasia, conotruncal heart defects, and facial dysmorphism, and its estimated incidence ranges from 1:3,000-to-1:4,000 live births.

Two aspects of the DiGeorge story intrigue me. First, confirming the illusory nature of categories, which some medical specialists guard jealously, here was DiGeorge, a paediatric endocrinologist, striding across the immunological landscape. Dare one suggest that porous, rather than sealed, interfaces between medical specialties would be more reflective of life’s complexities, and thus more beneficial to patients? Second, I was interested to read in his obituary of DiGeorge that Stafford writes: “Anne Lawlor, chairwoman of the 22q11 Ireland Support Group, said: ‘I feel a connection to the man because that is the diagnosis my daughter was given at 15, DiGeorge syndrome.’” Today, Anne Lawlor remains Chair of the 22q11 Ireland Support Group (22q11ireland.org). The group welcomes and encourages those affected by 22q11.2DS, and their families “with open arms and an empathetic ear, and by working to build a holistic care model that will help 22q11.2DS patients and their loved ones throughout their lives”.

Yes, but 22q11.2DS is a rare condition, and at a time of economic austerity its patient advocates should surely not expect to attract the levels of funding they might otherwise expect, right? Wrong. Yes, 22q11.2DS is rare… but it is not rare. This apparent contradiction is contextualised by Dr Shane McKee – Consultant in Genetics and Genomic Medicine at the Northern Ireland Regional Genetics Service – who, in a 2020 TED Talk entitled ‘Tanks, bikes, and genes’ explains that although rare disorders are defined as affecting fewer than one-in-2,000 people, there are thousands of rare disorders, with McKee citing evidence that one person in 17 has a rare disorder. Thus, rare disorders are relatively common, a point that those holding governmental purse strings must be persuaded to understand.

Ivan Illich (1926-2002) in his essay Disabling Professions (1977) suggests that a government “that bases its decisions on expert opinions given by professions might be government for, but never by the people”. And how refreshing it is to see Dr McKee consider “the democratisation of the genome” and learn how the families of those affected by rare – that is, common – diseases are themselves shaping events for the better. An outstanding example of collaboration between researchers and those with 22q11.2 DS was presented at the 17th International Conference on Integrated Care, Dublin, in May 2017 and later written up by Kerin, et al as ‘Hearing the lived experience of young women with a rare genetic disorder 22q11.2DS regarding integrated care’ in the International Journal of Integrated Care (2017; 17: A227, pp. 1-8). The paper was co-authored by Áine Lawlor, one of six young women with 22q11.2DS aged 21-to-35 years recruited to a ‘Young Experts by Experience Panel’ to help emphasise that “[t]he lived experience of young people with chronic disease has seldom been heard in health research despite the clear policy imperative to hear the voices of children and young people as service users and rights holders”. Forty years after Illich’s reference to professional experts determining government for the people, here is a non-professional expert Áine Lawlor helping to illuminate how government by the people might work and finding that a “participatory approach to research was an empowering process for young adult patients, which resulted in a compelling request to policy makers to enable integrated care for rare chronic diseases”.

University College Dublin’s Dr Suja Somanadhan and colleagues describe in HRB Open Research (2020, 3:13) how the Rare Disease Research Partnership (RAinDRoP) was established in 2018 “to bring together a wide variety of diverse voices in the rare disease community in Ireland and form a research partnership”. But meanwhile, as the International 22q11.2 Foundation  reminds us: “Healthcare providers need to have basic knowledge about the variable, multi-system, and changing nature of 22q11.2DS. Specialists from various disciplines need to provide coordinated care and tailor the treatment to suit the child. Family members and caregivers are an essential part of the care team and benefit from information and support.”