Paradoxical physiological responses to propranolol in a Rett syndrome patient: a case report

• Published in: BMC pediatrics Vol. 16; no. 1; p. 194
• Main Authors: Santosh, P J, Bell, L, Lievesley, K, Singh, J, Fiori, F
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 29.11.2016; BioMed Central
• Subjects: Adolescent; Adrenergic beta-Antagonists - pharmacology; Adrenergic beta-Antagonists - therapeutic use; Anxiety; Autism; Beta blockers; Brain research; Cardiac arrhythmia; Care and treatment; Case Report; Dosage and administration; Drug therapy; Electrocardiography; Epigenetic inheritance; Female; Girls; Health aspects; Heart Rate - drug effects; Humans; Hyperventilation; Mutation; Panic attacks; Patients; Pediatrics; Physiological aspects; Propranolol; Propranolol - pharmacology; Propranolol - therapeutic use; Rett syndrome; Rett Syndrome - drug therapy; Rett Syndrome - physiopathology; Scoliosis; Automatic monitoring of physiological parameters; Generalised anxiety disorder; MeCP2; Dysautonomia; Propranolol; Rett syndrome
• ISSN: 1471-2431; 1471-2431
• DOI: 10.1186/s12887-016-0734-3

Rett Syndrome (RTT), caused by a loss-of-function in the epigenetic modulator: X-linked methyl-CpG binding protein 2 (MeCP2), is a pervasive neurological disorder characterized by compromised brain functions, anxiety, severe mental retardation, language and learning disabilities, repetitive stereotyped hand movements and developmental regression. An imbalance in the sympathetic and the parasympathetic nervous system (dysautonomia) and the resulting autonomic storms is a frequent occurrence in patients with RTT. The prototypical beta blocker propranolol has been used to manage sympathetic hyperactivity in patients with RTT. A 13 year old girl with RTT was referred to the Centre for Interventional Paediatric Psychopharmacology and Rare Diseases (CIPPRD), South London and Maudsley NHS Foundation Trust. Her clinical picture included disordered breathing with concomitant hyperventilation and apnoea, epilepsy, scoliosis, no QT prolongation (QT/QTc [372/467 ms on automated electrocardiogram [ECG], but manually calculated to be 440 ms]), no cardiac abnormalities (PR interval: 104 ms, QRS duration: 78 ms), and generalised anxiety disorder (ICD-10-CM Diagnosis Code F41.1). She was also constipated and was fed via percutaneous endoscopic gastrostomy (PEG). To manage the dysautonomia, propranolol was given (5 mg and 10 mg) and in parallel her physiological parameters, including heart rate, skin temperature and skin transpiration, were monitored continuously for 24 h as she went about her activities of daily living. Whilst her skin temperature increased and skin transpiration decreased, unexpectedly there was a significant paradoxical increase in the patient's average heart rate following propranolol treatment. Here, we present a unique case of a paradoxical increase in heart rate response following propranolol treatment for managing dysautonomia in a child with RTT. Further studies are warranted to better understand the underlying dysautonomia in patients with RTT and the impact this might have on treatment strategies in rare disorders such as RTT.