Journal Article

The French national protocol for Kennedy’s disease (SBMA): consensus diagnostic and management recommendations

Vial, Christophe, Wahbi, Karim, Bede, Peter, Jublanc, Christel, Morélot Panzini, Capucine, Pradat, Pierre-François, Couratier, Philippe, Querin, Giorgia, Corcia, Philippe, Bernard, Emilien, Desnuelle, Claude, Salachas, François

2020

Overview

Background Kennedy’s disease (KD), also known as spinal and bulbar muscular atrophy (SBMA), is a rare, adult-onset, X-linked recessive neuromuscular disease caused by CAG expansions in exon 1 of the androgen receptor gene (AR). The objective of the French national diagnostic and management protocol is to provide evidence-based best practice recommendations and outline an optimised care pathway for patients with KD, based on a systematic literature review and consensus multidisciplinary observations. Results The initial evaluation, confirmation of the diagnosis, and management should ideally take place in a tertiary referral centre for motor neuron diseases, and involve an experienced multidisciplinary team of neurologists, endocrinologists, cardiologists and allied healthcare professionals. The diagnosis should be suspected in an adult male presenting with slowly progressive lower motor neuron symptoms, typically affecting the lower limbs at onset. Bulbar involvement (dysarthria and dysphagia) is often a later manifestation of the disease. Gynecomastia is not a constant feature, but is suggestive of a suspected diagnosis, which is further supported by electromyography showing diffuse motor neuron involvement often with asymptomatic sensory changes. A suspected diagnosis is confirmed by genetic testing. The multidisciplinary assessment should ascertain extra-neurological involvement such as cardiac repolarisation abnormalities (Brugada syndrome), signs of androgen resistance, genitourinary abnormalities, endocrine and metabolic changes (glucose intolerance, hyperlipidemia). In the absence of effective disease modifying therapies, the mainstay of management is symptomatic support using rehabilitation strategies (physiotherapy and speech therapy). Nutritional evaluation by an expert dietician is essential, and enteral nutrition (gastrostomy) may be required. Respiratory management centres on the detection and treatment of bronchial obstructions, as well as screening for aspiration pneumonia (chest physiotherapy, drainage, positioning, breath stacking, mechanical insufflation-exsufflation, cough assist machnie, antibiotics). Non-invasive mechanical ventilation is seldom needed. Symptomatic pharmaceutical therapy includes pain management, endocrine and metabolic interventions. There is no evidence for androgen substitution therapy. Conclusion The French national Kennedy’s disease protocol provides management recommendations for patients with KD. In a low-incidence condition, sharing and integrating regional expertise, multidisciplinary experience and defining consensus best-practice recommendations is particularly important. Well-coordinated collaborative efforts will ultimately pave the way to the development of evidence-based international guidelines.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adult / Age / Androgen insensitivity / Androgen receptor / Androgen receptors / Androgens / Antibiotics / Atrophy / Autophagy / Bulbo-Spinal Atrophy, X-Linked - diagnosis / Bulbo-Spinal Atrophy, X-Linked - genetics / Consensus / Cough / Diagnosis / Disease / Disease management / Dysphagia / Electromyography / Epidemiology / Evidence-based medicine / Genetic screening / Genetic Testing / Glucose metabolism / Glucose tolerance / Guidelines / Gynecomastia / Human Genetics / Humans / Hyperlipidemia / Intolerance / Kennedy disease / Life Sciences / Literature reviews / Male / Mechanical ventilation / Medical diagnosis / Medical research / Medicine / Medicine & Public Health / Motor neuron diseases / Motor Neurons / Natural history / Neuromuscular diseases / Pharmacology/Toxicology / Polyglutamine / Practice Guidelines as Topic / Proteins / Rare diseases / Rare neurological diseases / Rehabilitation / Speech therapy / Spinal and bulbar muscular atrophy / Trinucleotide repeats