Table 2.

Detailed approaches to management and therapy for RTT: genetics, neurology, cardiology, respiratory and urology

System/area	Common concerns and questions	Details and suggested approach	References
Genetics	MECP2 gene	For suspicion of RTT, MECP2 gene sequencing and MLPA testing are recommended. MLPA testing is needed to detect deletions otherwise missed by sequencing; this test is necessary if no abnormalities are found by sequencing. Referral to a geneticist or genetic counsellor is recommended to review recurrence risks and answer related questions. Genetic testing results are essential for enrolment in clinical trials. Referral to a Rett centre if feasible may be useful to provide multidisciplinary care and access to clinical trials.	16 85 86
Neurology	Seizures and spells	Refer to neurologist for seizures and spells suspicious for seizures, with follow-up every 6 months if treated with an anticonvulsant. It is difficult to differentiate between a non-epileptic Rett spell and a seizure (both may be present). Individuals can have multiple types of seizures. Seizure logs by the family are needed with careful description of events that includes frequency and duration. Videos of events are helpful to the neurologist. The neurologist may order a video electroencephalogram (EEG) to accurately characterise whether a type of event is a seizure or not. An overnight EEG may be necessary to capture sleep; an EEG is incomplete if sleep is not captured.	53–56
	Abnormal movements	Ataxic gait and an impaired spatial awareness (proprioception) are common. Stereotypical hand movements (hand wringing, mouthing and so on) are typical. These are often disruptive to hand use. Use of splints to elbows or hand guards, which may be prescribed by an OT, may be helpful to improve hand use. Initially, most individuals have low tone that progresses over years to high tone and dystonia. Neurologist or physiatrist may prescribe neuromuscular blockade or other medications to reduce tone to maintain function and prevent contractures.	67 68 87 88
Cardiology	Abnormal ECG	Yearly ECG to check for prolonged QTc interval which can develop at any time. Referral to cardiologist if the ECG is abnormal, who may consider further studies (Holter monitor, echocardiogram) or treatment. Avoid prescription of medications that can prolong QTc interval (ie, fluoxetine). A current ECG is recommended before anaesthesia.	49–52
	Poor circulation	Distal temperature asymmetries are common and thought to be autonomic in origin; no specific therapy is recommended.	61 89 90
Respiratory	Hyperventilation, air swallowing, breath-holding, blowing raspberries	Due to autonomic dysregulation, these may occur during the day. While not purposeful, they may be triggered by anxiety. Currently, there are no medications or treatments for these. If night-time apnoeas are present, check tonsils and consider ordering a comprehensive sleep study and related specialist referral. Breathing abnormalities may disrupt feeding.	62 63 91–93
Urology	Urine retention	Autonomic dysfunction can lead to delayed bladder emptying and bladder distension. If present, referral to urology may be needed. Constipation can increase risk of urinary tract infections. Toilet training can be achieved in some cases. Certain medications or poor fluid intake can cause increased risk of kidney stones.	69 70 See: 94

References not specific to RTT noted as ‘See’.

MLPA, multiplex ligation-dependent probe amplification; OT, occupational therapy; RTT, Rett syndrome.