What Every Internist-Endocrinologist Should Know about Rare Genetic Syndromes in Order to Prevent Needless Diagnostics, Missed Diagnoses and Medical Complications: Five Years of ‘Internal Medicine for Rare Genetic Syndromes’

Abstract

Patients with complex rare genetic syndromes (CRGS) have combined medical problems affecting multiple organ systems. Pediatric multidisciplinary (MD) care has improved life expectancy, however, transfer to internal medicine is hindered by the lack of adequate MD care for adults. We have launched an MD outpatient clinic providing syndrome-specific care for adults with CRGS, which, to our knowledge, is the first one worldwide in the field of internal medicine. Between 2015 and 2020, we have treated 720 adults with over 60 syndromes. Eighty-nine percent of the syndromes were associated with endocrine problems. We describe case series of missed diagnoses and patients who had undergone extensive diagnostic testing for symptoms that could actually be explained by their syndrome. Based on our experiences and review of the literature, we provide an algorithm for the clinical approach of health problems in CRGS adults. We conclude that missed diagnoses and needless invasive tests seem common in CRGS adults. Due to the increased life expectancy, an increasing number of patients with CRGS will transfer to adult endocrinology. Internist-endocrinologists (in training) should be aware of their special needs and medical pitfalls of CRGS will help prevent the burden of unnecessary diagnostics and under- and overtreatment.

Patients with DeSanto–Shinawi syndrome: Further extension of phenotype from Italy

“…Patients with complex rare genetic syndromes experience combined medical problems that affect multiple organ systems. Rosenberg et al (2021) observed that 89% of rare genetic syndromes are linked with endocrine problems; according to the European Registries for Rare Endocrine Conditions, there are more than 440 distinct rare diseases that affect the endocrine system (Reincke & Hokken‐Koelega, 2021). To avoid inaccurate or missed diagnoses, we recommend surveillance for individuals with WAC ‐related intellectual disability (Varvagiannis et al, 2017); moreover, we suggest including an endocrine evaluation for hirsutism, hyperandrogenism, and oligomenorrhea and performing routine procedures to assess pituitary function to determine the most appropriate treatment to improve the patient's quality of life.…”

Comprehensive genetic testing approaches as the basis for personalized management of growth disturbances: current status and perspectives

“…For many of the growth disorders, there is limited knowledge about their natural history, development of comorbidities, and best overall management. A multidisciplinary approach with a clinical algorithm was recently published ( 59 ). This can be improved by centralized care, registries, or collaborations in networks such as the ERN-Endo.…”

A Review of Prader–Willi Syndrome

“…The inherent variability in presentation and the wide range of non-specific clinical features associated with PWS generate a large differential diagnosis list when evaluating these patients including genital hypotonia, myotonic dystrophy, spinal muscular atrophy, fragile-X syndrome, and FG syndrome [40]. PWS that is identified later in life also necessitates the consideration of Klinefelter syndrome; Bardet-Biedl syndrome; Albright hereditary dystrophy; Börjeson-Forssman-Lehmann syndrome; maternal uniparental disomy chromosome 14 (Temple syndrome); copy number variants (CNVs) including del1p36, del2q37, and del6q16; Angelman syndrome; and Cohen syndrome, especially in cases in which the dominant feature is intellectual disability combined with non-specific obesity [40][41][42].…”