Nervous System

  Gastroenteric Renal/Urological  
Symptoms What to look for/be aware of Investigation & treatment and/or referral pathway Further reading

Early developmental impairment (NB falls into diagnostic criteria and seen in early development)

  • Early significant delay is not typical for classic Rett but does occur in the congenital variant. Typical Rett will have some relatively minor delays but have a clear period of regression where skills are lost.
  • Documentation of milestones - gross motor, fine motor, speech comprehension, socialisation.
  • Referral to appropriate services.
  • Check vision and hearing.

Muscle Tone and Tone Management

  • Variable from low to high tone but frequently outside the normal range. See also autonomic dysfunction – hypertonia.
  • Referral to physiotherapy.
  • Holistically assess with MDT for neurological disorders.
  • Check positioning – standing (frame), appropriate supported seating, lying (sleep system).
  • Check for co-morbidities (constipation) and medications (Benzodiazepines) that alter tone positively or negatively.
  • Massage and stretching of muscle groups should be part of a comprehensive postural care plan (for people with Rett of all ages) under the guidance of a therapy team.
  • Pharmacological tone management.

Dystonia

  • Focal or generalised - involuntary spasms and contractions.
  • The movements are often repetitive and take on unusual and awkward postures.
  • They can also be painful. See also autonomic dysfunction - hypertonia
  • Typical medication used for dystonia: Trihexyphenidyl, baclofen, gabapentin, clonidine, benzodiazepines.
  • NB – There is no strong evidence base to guide this: Typical medication used for managing spasticity: baclofen, gabapentin, benzodiazepines, tizanidine

Spasticity

  • Caution with benzodiazepine use, given risks of increasing secretions, respiratory depression, tolerance and dependency.
  • Botulinum toxin can be considered for focal elements of high tone (either spasticity or dystonia).

Altered Tissue Properties

  • Over time, any abnormal muscle contraction can give rise to changed tissue properties – with changes in the viscoelasticity (viscosity – measure of resistance to stretch, elasticity – tendency to return to original shape/length) that make muscles feel stiffer. This ultimately leads to fixed musculoskeletal deformity.
  • Close therapy review regarding risk of development of fixed musculoskeletal deformity, with prompt referral to orthopaedic surgeons if concerns arise.

Epilepsy

  • May be present in up to 70% of people with Rett Syndrome but majority of people with Rett will have abnormal EEG.
  • Often starts around age 4/5 years.
  • Huge variation in type/frequency of seizures including gelastic seizures.
  • First hand description +/- video recording to make a confident diagnosis of epilepsy but 48 hour EEG with video telemetry and sleep study at baseline, including neurophysiological, cardiological and respiratory measurements at minimum.
  • Seizures triggered by hypoxia/sleep disturbances may be better managed by primarily addressing these triggers.
  • AEDS based on type of seizure.
  • Recommended good practise for children and young people with epilepsy to have a person specific epilepsy care plan. See guidance in further reading.
  • Ketogenic diet can be helpful for some.
  • All children and young people with Rett Syndrome and refractory seizures should be able to access assessment for potential epilepsy surgery. It is unlikely that resective surgery will be appropriate, but Vagal Nerve Stimulation may be of potential benefit.

Paroxysmal episodes not due to epilepsy

  • May be linked to autonomic dysfunction.
  • 48 hr EEG with video telemetry and sleep study to distinguish from seizures.

Movement Disorder and Motor Planning

  • Disturbance in motor planning that impacts on all purposeful tasks and movements.
  • Referral to Occupational Therapy and Physiotherapy.
  • Verbal Cueing, avoid direct questions and instructions, acknowledge time needed to respond.
  • Difficulties with motor planning can impact the ability to change from one position to another.
  • Comprehensive physio plan involving all caregivers and professionals re postural transitioning should be put in place in order to maintain independence.

EBAD - Emotional, Behavioural and Autonomic Dysregulation (Emotional - Assess changes from baseline) Anxiety/Panic

  • Generalised anxiety – behaviours not usually seen in a neurotypical person of the same age may be anxiety – related. Look for rapid breathing, breath holding, worsening hand-wringing.
  • Can also drive seizures and dystonia. Episodic anxiety (panic) – episodes lasting up to 30 minutes where other behaviours/breathing symptoms (and everything else, becomes significantly worse.
  • Appear distressed/terrified.
  • See Figure 2 in Singh and Santosh Emotional Dysregulation.
  • All-encompassing approach whereby (i) emotion, (ii) behaviour and (iii) autonomic function needs to be considered holistically in patients with Rett.
  • Explore other potential untreated issues, which could be causing pain leading to distress/anxiety, including but not limited to, reflux, gall-bladder, UTI/Urine retention, dental, broken bones/injury.
  • Conventional anxiety treatments (e.g. SSRIs) are often not successful and can lower the seizure threshold.

See also Paroxysmal episodes not due to epilepsy

  • Mood lability.
  • Loss of interest in normal day to day activites.
  • Children and adults with Rett Syndrome are as vulnerable to typical sadness triggers as general population. Consider current/recent personal circumstances when reviewing EBAD issues.
  • Autonomic Dysregulation
    • Breathing difficulties such as apnoea and rapid breathing.
    • Cardiac problems – sudden swings in heart rate (tachycardia/bradycardia).
    • Gastrointestinal problems – constipation and loose stools.
    • Flushing and sweating.
  • Behavioural Dysregulation
    Repetitive rocking, screaming, scratching, agitation, sleep problems.
  • Benzodiazepines for control of seizures should be used with extreme caution as may lead to respiratory depression and could be life-threatening in individuals with Rett Syndrome.
  • Drugs which may prolong the QT interval such as common antibiotics or other psychiatric medications should be used with caution.
  • Referral to Centre for Interventional Paediatric Pharmacology and Rare Diseases.
  • Explore all possible physical causes for sudden changes in mood or behaviour. Acute medical conditions common in Rett Syndrome include UTIs, urinary retention, gall bladder sludge and stones.
  • Pharmacological interventions in a specialist setting only in case of effects on the autonomic symptoms.
  • Helpful if parents/carers can make video recording of episodes.
  • 48 hour EEG with video telemetry and sleep study should be done at baseline, including neurophysiological, cardiological and respiratory measurements (at minimum) to distinguish from seizures.

Mood Problems Including Depression

  • Low mood: Would the presentation be usual for a neurotypical person of the same age? If not, then the problem should be treated.
  • Look for loss of interest/enjoyment in previously pleasurable activities, reduced attempts to communicate, increased lethargy, increased distress – assess degree of change from their own baseline and degree of impairment.
  • Establish if the problem is related to poor quality sleep. Refer for sleep study including neurophysiological, cardiological and respiratory measurements to identify any sleep issues which are not being addressed.
  • Can be prolonged in some people or present in some for some of the time.
  • Mood lability common; uncontrolled giggling/laughing spells.
  • Explore all possible physical causes for sudden changes in mood or behaviour. Acute medical conditions common in Rett Syndrome include UTIs, urinary retention, gall bladder sludge and stones.
  • May also experience worsening seizures, gastrointestinal symptoms, tachycardia, blood pressure, sweating. Conservative management techniques – PBS, music, environmental strategies, distraction, calming/soothing techniques suitable to the individual.
  • Conventional treatments (e.g. SSRIs) need to be used very cautiously and may not be very successful.
  • Benzodiazepines should not be given – this may lead to respiratory depression and could be life-threatening in individuals with Rett Syndrome.
  • Pharmacological interventions in a specialist setting only in case of effects on the autonomic symptoms.

Behavioural Dysregulation Hand Stereotypies

  • Separated hands: Tend to improve with time. [Mouthing, hair pulling, pill rolling tremor related to dystonia. One hand behind the neck, castanets, twisting two or three fingers, flapping, tapping, “Sevillana” sequential flexion of metacarpophalangeal and interphalangeal joints 5th to 2nd, hand twirling, hand gaze.]
  • Joined hands: Tend to worsen with time and may progress to self-injurious behaviour. [Washing/wringing/clasping, clapping, mouthing]
  • Refer to OT/physio depending on level of impairment.
  • Look at splinting options – Bamboo splints can be helpful.
  • Neoprene Gloves.

Phonic stereotypy, self-stimulating behaviour, self-injury, agitation

  • Other stereotypies:
  • Arms: Repetitive and rhythmic flexion of the arms.
  • Legs: Intermittent leg elevation and tapping of the floor.
    • - Toe walking, jumping
    • - Feet twirling
    • - Whole body: trunk rocking, shifting weight from one leg to the other
    • - Repetitive sounds
    • - Repetitive words or phrases
    • - Rocking, self-touching
    • - Scratching, biting, mouthing, wringing causing skin breakdown, head banging
    • - Behavioural disturbance associated with distress.
  Gastroenteric Renal/Urological