ESPE Abstracts

Introduction: Patients with rare genetic syndromes (RGS) often have a combination of hormone deficiencies, organ problems and neurodevelopmental disorders. Due to excellent paediatric care, a growing number of patients is reaching adult age. Transition of these patients to adult health care system has proved to be challenging. Due to the rarity and complexity of their syndromes, patients with RGS often suffer from medical complications due to needless diagnostics, unnecessary treatments and missed diagnoses. In 2014, paediatric endocrinologists expressed the urgent need for multidisciplinary follow-up for adults with RGS in order to improve quality of healthcare for this vulnerable patient group.

Materials and Methods: To launch the Centre for Adults with RGS, a multidisciplinary team was established consisting of an endocrinologist, neuropsychologist, physician for intellectual disabilities, dietitian, physiotherapist, nurse practitioner and geriatrician. Patients were referred from all over The Netherlands, triaged by the specialized nurse practitioner, discussed at the multidisciplinary board and seen at the outpatient clinic. Systematic screening included medical questionnaires (completed by patient and/or caregivers) and clinical assessment. At the outpatient clinic, a structured interview, complete physical examination, biochemical measurements and, if indicated and feasible, additional tests were performed. Patients were grouped according to their growth, metabolism, aging and brain phenotype. If consented, biochemical samples were biobanked.

Results: Since 2014, we have provided multidisciplinary care to more than 1200 new patients, with more than 120 syndromes. Growth phenotypes ranged from severe dwarfism (adult height 130 cm) to generalized overgrowth (adult height 208 cm). Metabolic features ranged from extreme insulin sensitivity to hyperinsulinism and from severe underweight (BMI 13 kg/m²) to severe obesity (BMI 78 kg/m²). Aging phenotypes included premature aging, progeroid syndromes and DNA repair disorders. The spectrum of sex chromosomal disorders ranged from XXXXY to XO and from XY females treated with oestrogens to XX males treated with testosterone. Brain phenotypes ranged from severe intellectual disability to extreme high intelligence, ADHD, autism and epilepsy. We biobanked over 400 samples, covering different cellular pathways.

Discussion: In the past 10 years, the centre for adults with rare genetic syndromes has provided unique multidisciplinary care to over 1200 patients with genetic variants in numerous pathways. Apart from improving quality of life of these patients, the combination of detailed phenotypic and biobanked materials offers unique possibilities for clinical and translational research. During our presentation, we will give a patients-per-pathway overview, in which striking phenotypes are discussed in the light of the affected pathways.