What is 22q11.2 deletion syndrome?
22q11.2 deletion syndrome, also known as DiGeorge Syndrome or VCFS (Velo-Cardio-Facial-Syndrome) is a multi-system condition, extremely variable, often poorly recognised/understood and occurs in 1 in every 2 – 4,000 births worldwide1.
In the absence of the more serious symptoms e.g. congenital heart defects or thymus gland abnormalities 22q often comprises a constellation of more minor disparate symptoms. Cleft palate, delayed acquisition of speech, difficulty in feeding and swallowing, hearing, learning disabilities, behavioural problems, hyperactivity and psychiatric disorders are all features of this multi-system condition. Complications arising from calcium and Vitamin D deficiencies are also common. A late diagnosis of 22q is not unusual and can occur at any age2.
Living with 22q for parents early childhood is often characterised by multiple appointments, lack of awareness among health-care professionals, lack of coordinated care and concerns about children in school settings where knowledge of the cognitive profile and subsequent educational needs is scarce.
22q11.2 deletion syndrome is a multi-system condition requiring a multi-system approach. In the absence of a dedicated clinic the care-coordinator joining all the necessary components together is in many instances the mother. As in my case, she also becomes an amateur researcher and will become extremely knowledgeable about 22q and how it impacts her child. She will become the quintessential parent expert that professionals will either embrace or keep at arm’s length. There is nothing more helpful to a mother than to meet with a health care professional that says “no, I’ve never heard of 22q but I’m very willing to find out more and I’m more than happy to work with you to provide the best care that I can for your child”. Conversely, for the mum who arrives into the doctor or consultant with the international 22q care guidelines to be told dismissively “that’s not how we do things around here” is very unhelpful indeed. The most unhelpful thing of all is to come away from any professional meeting feeling that your concerns as a parent have not been heard and taken seriously.
We live in an information era where previously inaccessible knowledge is now readily available to all. Furthermore, this information is easily shared. When a parent-community meets, either online or at events and exchange knowledge resources and experiences something wonderful occurs. Isolation, loneliness and fear decrease and is replaced by validation, empathy, understanding, recognition, bonding, relief and basic peer-to-peer support. This in turn boosts parent’s confidence and often-flagging energies. The more knowledgeable parents become the more empowered they feel about being their child’s best advocate. Having a well-established 22q community is a priceless gift for a parent on any part of the 22q ‘journey’. Those who have trod the path become mentors for the newly diagnosed who in time become mentors themselves.
It’s very difficult for anyone not well versed in genetic chromosomal conditions to recognise 22q. It is especially difficult for parents with no medical/clinical knowledge. Mothers invariably will have a sense of something ‘not being right’ but vague concerns like this are often dismissed. Although subtle, 22q does have facial dysmorphism but unlike Down syndrome is not as easily visibly recognisable. Very rarely are the minor disparate symptoms dot-joined and even more rarely is a genetic condition suspected. In the end either a clinician and/or a parent might speculate about a diagnosis of 22q but the only definitive way to find out is with genetic testing.
In my own personal experience, chronic constipation, feeding difficulties, frequent respiratory infections and global developmental delay were characteristic of my daughter’s early life. Prior to her diagnosis at 15 when the genetic FISH test became available her only diagnosis at 6 was of ‘mild mental retardation cause unknown’.
Such is the immense variability of 22q however that there are cases where very few physical symptoms are present. Some children are diagnosed because of speech and language delay or emotional/behavioural problems that prove problematic in school.
In the absence of the more serious symptoms clinically 22q is often described to parents as ‘mild’. Clinically this may make sense, to the lay-person however a mild diagnosis is perhaps a very deceptive one to receive. As parents we often take it to mean mild when in fact it is only ever mild when compared to something more serious. When we compare our child, teen or adult to a same-aged neuro-typical person we very quickly realise that there is nothing ‘mild’ about 22q at all. Hardly any parents are given accurate information on mental health issues and very few children receive baseline psychiatric assessments at an early age. And sure why would you need all that if you’ve received a ‘mild’ diagnosis?
As children age ongoing concerns revolve around mental health and uncertainties about the future in areas of work, relationships and independent living. Children grow up, not out of 22q, and over the lifespan an individual may need to see several specialists and health care professionals. Currently there are no dedicated services for adults with 22q anywhere in the UK or Ireland.
Mental Health and 22q
Mental health issues prevail throughout the lifetime of individuals with 22q. In stark contrast to the general public rates of ADHD, ASD, anxiety and mood disorders are greatly elevated in the 22q population. Psychotic symptoms arising in approx. 50% of adolescents progress to psychotic disorders in 10-25% of individuals.
- Attention Deficit Hyperactivity Disorder (ADHD) is the most prevalent MH diagnosis in children with 22q3.
- Schizophrenia occurs in ∼25% of individuals with 22q11.2 deletion syndrome, the strongest known molecular genetic risk factor for schizophrenia4.
Sleep and 22q
Problems with sleep are very common in patients with 22q11.2 deletion syndrome5. Sleep disordered breathing, including obstructive sleep apnea is seen in about 50% of patients with 22q in craniofacial clinic compared to about 11% in the general population. There are many contributing factors: facial anatomy and palate repairs, and medical issues, for example cardiorespiratory problems. Sleep can also be disrupted with night leg pains. Many patients have anxiety and difficulty falling asleep at bedtime.
Relationship with 22q11.2 deletion syndrome, sleep and mental health.
What follows is a summary of both my own parental ‘lived experience’ of 22q and more than a decade of interacting with and listening to other parents of children with the condition. It is an extraordinarily variable condition and although individuals may have similar issues, no two are the same. Sleep and mental health are inextricably intertwined and may co-exist alongside a number of other symptoms which are all interacting with each other at any given time. Essentially, it’s a ‘which comes first: the chicken or the egg?’ situation. Are mental health issues causing the sleep problems or are physical symptoms the reason for poor sleep? Are physical reasons sometimes overlooked and/or untreated? Or, is it a combination of both with a swing to either one or the other depending on what’s happening in the child’s life at any given time?
Individuals with 22q11.2 deletion syndrome are born with a genetic predisposition to mental ill-health. The majority are faced with a myriad of physical health issues, learning difficulties and a variety of mental health concerns. Poor sleep and sleep disturbances are more common in childhood but can occur at any time and for varying reasons and for some, they can remain a problem over the lifespan. There is a thriving online international 22q community and many parents in these forums speak of difficulties with getting children to sleep, night terrors and wakefulness. Anecdotally developmental delays for some appear to extend to the age when children begin sleeping in their own beds and there are several reports of children waking and coming into the parents’ bed during the night. Parents also report that sleep issues sometimes resolve on their own, with melatonin (doesn’t work for everyone) or continue into adolescence. Paradoxically sleep issues previously resolved can return in adolescence and may be school related.
The most common reasons for sleep disturbances cited by parents are sleep apnoea due to floppy larynx, undiagnosed reflux, separation anxiety, social anxiety / anxieties related to school, leg pains and gastrointestinal issues. Hip pain and sore peg-tube site irritation were also mentioned.
Although mental health issues in relation to 22q are well documented in the literature there remains a considerable gap between translating that knowledge into practical applications for parents and families. In addition information given to parents with regard to psychiatric manifestations of 22q is scant both at time of diagnosis and at later stages6.
The complex interactions between physical and mental health symptoms coupled with an often unaccepting environment that does not recognise the immense anxiety that children with 22q may be under does not augur well for successful long-term resolution of sleep and/or mental health issues. Ideally this vulnerable population of children require careful monitoring with ready access to appropriate therapies and mental health services. Greater awareness of this poorly-understood condition with coordinated care across health, education and social-care systems would likely allow each individual to reach their potential and cope with the (ab)normal stresses of living life with 22q11.2 deletion syndrome. The WHO definition of mental health applies as much to them as it does to anyone else:
Mental health is defined as a state of well-being in which every individual realizes his or her own potential, can cope with the normal stresses of life, can work productively and fruitfully, and is able to make a contribution to her or his community.
- Vo, O. K., McNeill, A., & Vogt, K. S. (2018) The psychosocial impact of 22q11 deletion syndrome onpatients and families: A systematic review. American Journal of Medical Genetics Part A, 2018, 00, 1-11.
- Palmer, L. D., Butcher, N. J., Boot, E., Hodgkinson, K. A., Heung, T., Chow, E. W. C., Guna, A., Crowley, T. B., Zackai, E., McDonald-McGinn, D. M., & Bassett, A. S. (2018) Elucidating the diagnostic odyssey of 22q11.2 deletion syndrome. American Journal of Medical Genetics Part A, 2018, 176(4), 936-944.
- Niarchou, M., Calkins, M. E., Moore, T. M., Tang, S. X., McDonald-McGinn, D. M., Zackai, E. H., Emanuel, B. S., Gur, R. C., & Gur, R. E. (2017) Attention Deficit Hyperactivity Disorder Symptoms and Psychosis in 22q11.2 Deletion Syndrome. Schizophrenia Bulletin, 2017, Epub ahead of print.
- Van, L., Boot, E., & Bassett, A. S. (2017) Update on the 22q11.2 deletion syndrome and its relevance to schizophrenia. Current Opinion in Psychiatry, 2017, 30(3), 191-196.
- Massachusetts General Hospital (2018) 22q11.2 Deletion Syndrome Clinic. Retrieved from: http://www.massgeneral.org/children/services/treatmentprograms.aspx?id=1815
- Talcott Baughman, S., Morris, E., Jensen, K., & Austin, J. (2015). Disclosure of psychiatric manifestations of 22q11.2 deletion syndrome in medical genetics: a 12-year, retrospective chart review. American Journal of Medical Genetics Part A, 2015, 167A(10), 2350-2356.
- DiGeorge syndrome (22q11 deletion) – NHS
- ‘Diagnosis was like a lightbulb going on’
- 2 deletion: the most common syndrome you have never heard of
- Obstructive Sleep Apnoea Syndrome in Children with 22q11.2 Deletion Syndrome after Operative Intervention for Velopharyngeal Insufficiency
- Identifying patterns of anxiety and depression in children with chromosome 22q11.2 deletion syndrome: Comorbidity predicts behavioral difficulties and impaired functional communications
- How treating sleep may ease all forms of autism
- 22q11 Ireland
- The International 22q11.2 Foundation
- 22q11.2 Society