by Maria Giovanna Faiella
The little girl’s diagnostic odyssey, which lasted 8 years between tests, visits and hospitalizations in hospitals throughout Italy, ended only thanks to the exome test, which could soon be paid for. 400 patients worldwide; “networked” families to support research
Silvia, 11 years old, has CTNNB1 Syndrome (named after the mutated gene), a very rare and insidious disease from which 27 people (mostly children) suffer in Italy and around 400 in the world. She was diagnosed only four years ago, after a long wandering around hospitals, far from home, to undergo continuous tests, visits, hospitalizations, in search of the name of the diseasetherefore of a possible cure.
«We already had the suspicion that Silvia had an illness at the age of eight months because the little girl didn’t have control of her trunk and couldn’t sit up; from there the ordeal began – says the mother –. Despite an endless series of diagnostic tests, she was unable to identify the disease. We live in Calabria and for eight years we wandered around hospitals all over Italy, incurring unimaginable costs, economic (travel, hotels, etc.) but above all human because, when you see your daughter feeling ill without understanding the reasons, you are one step away from psychological collapse” .
Genetic tests are fundamental for diagnosis
Silvia’s family decides to have the little girl examined by one of the most expert geneticists in the world, Bruno Dallapiccola.
«The professor prescribed the analysis of the exome, which was still not very widespread at the time, which was done as a trio to the little girl, to me and to my husband at the Bambino Gesù pediatric hospital in Rome, one of the few in Italy to carry out the exam in those years – recalls mother Mirella –. It took some time to get the results, but we finally knew the cause of all our daughter’s problems and a name was given to the rare disease that had affected her, caused by a mutation in the CTNNB1 gene. The odyssey to get the diagnosis thanks to this genetic test, the only one capable of identifying it, was over.”
The exome and other fundamental genetic tests for the diagnosis of rare and very rare diseases, until now prescribed exemptly, thanks to the use of a generic code, could soon be paid for as they have not been included in the new nomenclature of outpatient specialists (services in scope of the LEAs, the essential levels of assistance), which will come into force in January 2025 after yet another postponement (we talked about it here).
Knowing the name of the disease is the first step to understand if there is a cure or the possibility for researchers to develop new therapies, but also to receive adequate assistance, in order to slow down the course of the pathology and allow patients to have a quality of acceptable life.
That mutated gene
CTNNB1 Syndrome manifests itself with multiple variants; depending on the degree of alteration or mutation of the gene, the types of disorders and their severity can vary from child to child. The disease can cause neuro-motor delays, intellectual disability, language impairment, trunk hypotonia and spastic hypertonia/diplegia of the limbs, especially the lower limbs, vision and behavioral disorders.
The loneliness (and strength) of families
«Having the diagnosis is fundamental – underlines Mirella –. After the initial shock of discovering that there is no cure for this ultra-rare disease, we started looking for other families, on the internet and on social media; so we found an international Facebook group, in which the parents of two Italian children with the same disease as our daughter were registered. It meant emerging from that condition of terrible solitude, comparing ourselves with other families, becoming aware, for better or for worse, of what awaited us.”
The exchanges of emails and telephone numbers begin; the chatter on social media helps to find other Italian children with this syndrome. The parents join forces and, to raise awareness of the syndrome and encourage scientific research on the symptoms and treatment possibilities, they form an Association, CTNNB1 Italiawhich today also makes use of a multidisciplinary technical-scientific committee.
«Since then – reports Mirella, who is also the president of the Association – other families have contacted us from different regions and today we have reached 27 patients in Italy with CTNNb1 syndrome».
Hope in research
Associations have been formed in various countries around the world also to stimulate and support research projects on the disease.
The president of CTNNb1 Italia reports: «Two scientific studies on the disease have been launched, one in Slovenia, the other in the United States. Now, finally, a pilot project coordinated by the Gaslini Institute and the Italian Institute of Technology of Genoa has also been launched in Italy to explore, with the help of artificial intelligence, new potential pharmacological treatments for CTNNb1 Syndrome. The hope is at least to improve the quality of life of our children: it is their right, like any other sick person.”
Parents and growing children are confident in the research that continues. The families of CTNNb1 Italia have mobilized to support the Italian project with a fundraiser, also on the platform GoFoundMe.
The Association is organizing the first international conference in Italy which will be held on 6 and 7 September in Acri, in the province of Cosenza: an opportunity to take stock of research with researchers and clinicians from Italy and other countries, but also to exchange information between parents.
Unrecognized disease
The pathology is not recognized as a rare disease by the National Health Service as it is not included in the list of rare diseases Annex 7 to the Essential Levels of Caretherefore it does not have its own code which gives the right to exemption from the ticket for all appropriate services for the treatment and monitoring of the pathology and for the prevention of further aggravations, nor to specific protections and rights provided by law, at a national level, for rare or very rare patients.
Lack of assistance
There is also a lot to be done on the assistance front. Silvia’s mother says: «According to the indications of the Bambino Gesù specialists who follow my daughter, she would need to do physiotherapy, cognitive-behavioral therapy, speech therapy, occupational therapy. But our local health authority no longer guarantees these therapies now that she is 11 years old. As they grow, these patients become almost invisible and the therapies are the responsibility of the family. But the little girl is not cured, on the contrary: she risks getting worse. In recent years, my daughter has had three fractures following trivial falls – says Mirella -. Since you have spasticity in the lower limbs (excessive stiffness), with a loss of perception of your motor activity, you may lose your balance and fall. Therefore, rehabilitation is fundamental for her, but she is no longer able to access it at the expense of the health service. If a family cannot afford private care, are these children abandoned? We parents ask that our children be guaranteed adequate healthcare – like all other patients – and holistic care because, unfortunately, they will never stop being sick. And support for families who find themselves facing enormous difficulties alone would also be necessary.”
Good practice
The care of patients can change from Region to Region, sometimes even from Local Health Authority to Local Health Authority. There are also positive experiences.
«The scientific literature for CTBNN1 is scarce and not homogeneous – says Dr. Fabrizio Paolini, child neuropsychiatrist of the Fondazione Inclusione Salute e Cura Roma Litorale ets, a highly specialized body accredited with the Lazio Region Health Service, which deals every day with over 450 children with disabilities –. Our center has therefore attempted to personalize the neuropsychomotor rehabilitation process and model it on the developmental profile and clinical picture, intervening early, with specific therapy, on the delay in psychomotor acquisitions – which represent one of the characteristics of the syndrome – and, secondly , adapting the therapy to the expected development in that particular genetic profile. Among the characteristics linked to CTBNN1 there is also an important tactile and auditory hypersensitivity which makes everyday life difficult, for example: dressing the child, making him wear shoes and socks, putting his feet on the ground or the presence of medium/high sounds . Other interventions – continues Dr. Paolini – concern the acquisition of basic neuropsychomotor skills, the expansion of the entire repertoire of action patterns to also strengthen the language part – compromised by CTBNN1 – and the management of a series of disorders of behavior. Through neuropsychomotor intervention it is essential to accompany parents in understanding the skills and not just the difficulties of their child, so as to define a true therapeutic alliance which is fundamental to obtaining the results achieved.”
May 9, 2024 (modified May 9, 2024 | 10:38)
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