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J Neurol Neurosurg Psychiatry. 2007 June; 78(6): 659–660.
PMCID: PMC2077955

Möbius syndrome in association with the REM sleep behaviour disorder

We report a 34‐year‐old woman with Möbius syndrome in association with lifelong sleep disturbance diagnosed as rapid eye movement (REM) sleep behaviour disorder (RBD). RBD proved treatment resistant and the possible structural reasons for this are discussed.

Case history

The patient was a 34‐year‐old woman who was noted at birth to have bilateral abducens nerve palsy, complete facial diplegia, club feet, malformation of the right upper limb and chest wall with an underdeveloped right hand and an absent pectoralis major. These abnormalities were non‐progressive and a diagnosis of Möbius syndrome was made based on the characteristic clinical features. The Poland anomaly (pectoralis major hypoplasia and mammary hypoplasia) is associated with 13% of cases of Möbius syndrome.1

From birth, the patient's mother noted sleep disturbance with brief crying and vocalisation as well as twitching arm and leg movements during sleep. The sleep disturbance became more marked over time and by the age of 3 years until the current day she has suffered episodes of screaming and abnormal movements occurring in the second half of the night on a nightly basis, usually between 02:00 and 04:00. Her mother described screaming with non‐stereotyped, flailing movements of her arms and legs lasting several minutes. The patient's legs often moved as if running in the bed. She had injured both herself and her mother when restrained during an attack and was initially confused after being woken.

The history from the patient was of persistent unpleasant dreams, with recurring themes. Examples included being chased through rooms with a gun and being hunted by guards in a concentration camp. The dreams did not change in a different environment but increased during menstruation and stressful life events.

There was no other past medical history; in particular there was no history of snoring, restless legs syndrome or sleepwalking. There was no family history of any psychiatric or sleep disorder. She was a teetotal non‐smoker.

Investigations

A diagnosis of RBD was made on the basis of her clinical description and she was investigated at Papworth Hospital. MRI of her brain with axial T1 weighted, T2 weighted and fluid attenuated inversion recovery sequences were normal, with no pontine abnormality seen. Routine 12 lead EEG while waking and drowsy was normal.

She underwent polysomnography on two consecutive nights using a standard protocol including video recording, sleep EEG (leads C3‐A2, O1‐A2), electrooculogram, and submental and bilateral anterior tibialis electromyography (EMG). Respiratory effort, airflow and oxygen saturation were measured to exclude sleep apnoea syndrome. Sleep stages were scored according to standard criteria in 30 s epochs. Sleep latency, sleep efficiency and percentage of stage 1, stage 2, stage 3, stage 4 and REM to total sleep time were recorded.

There was no sleep disordered breathing or periodic leg movements of sleep. REM sleep was difficult to stage because the facial diplegia and opthalmoplegia affected interpretation of the submental EMG and electrooculogram. Her sleep stages corresponded to 90 min cycles with clearly defined slow wave sleep and at 02:15 and 04:30 on the second night during non‐slow wave sleep she had brief episodes with vocalisation and some flailing movements of her right arm (fig 11).

figure jn105494.f1
Figure 1 Sleep staging from the polysomnogram is shown, with wake (WK), movement (MVT), rapid eye movement (REM) sleep and the non‐REM sleep stages, S1, S2, S3 and S4. There was some delay before the patient fell asleep but the overall ...

Treatment

The patient tried numerous medications sequentially over many years without benefit. In order, clonazepam, melatonin, carbamazepine, sertraline and temazepam were used at therapeutic doses, each for at least 3 months. None of the medications decreased the disturbing dreams. Cognitive behavioural therapy was also unsuccessful.

Discussion

Möbius syndrome was initially defined as congenital facial diplegia and bilateral abducens nerve palsies. The description has since been broadened as many patients have other cranial nerve palsies, with variable opthalmoplegia, bulbar dysfunction and tongue atrophy all seen. Musculoskeletal abnormalities occur in one third of patients with clubfeet, the commonest deformity, but brachydactly, arthrogryposis and the Poland anomaly are also seen.1

The pathogenesis of Möbius syndrome has been debated but simultaneous limb malformations with cranial nerve dysfunction suggest disruption of normal morphogenesis during a critical period in the development of the embryonic structures of these regions. In a review of 37 patients with Möbius syndrome, the authors concluded that the widespread involvement of various motor nuclei and axons made it more likely to be a syndrome of rhombencephalic maldevelopment, rather than an isolated cranial nerve or nuclear developmental disorder.1 Imaging studies showing a variety of brainstem anomalies, including absence of the facial nerve, support this theory.1

Typical idiopathic RBD affects elderly males, often in association with neurodegenerative diseases such as Parkinson's disease and dementia with Lewy bodies. Animal studies indicate that the pedunculopontine region of the upper brainstem is involved. RBD is usually well treated with clonazepam.2

It is possibly surprising that a disorder that causes brainstem abnormalities does not produce abnormalities of REM sleep more frequently. None of a large cohort of patients enrolled into a specialist Möbius clinic complained of disturbing dreams (Padberg GW, personal communication, 2006). Sleep disturbance in Möbius syndrome has been reported in association with both central and obstructive sleep apnoea and thought to be secondary to palatal dysfunction.1 There are no individual reports of RBD in association with this condition in the literature although there are reports of other patients with REM abnormalities,3,4 suggesting that the variable developmental, pontine disorder in Möbius syndrome can cause REM disturbance if the critical neural networks within the pedunculopontine nucleus are affected. Secondary causes of RBD with structural pontine lesions support this theory.5 It is also possible that the condition is underreported or underdiagnosed and that more cases will emerge as RBD becomes more widely recognised.

The description of the stereotyped disturbing dreams with dream enactment in the absence of other causes of sleep disturbance on the polysomnography is characteristic of RBD, but atypical features include the early age of onset and treatment resistance. The young age of onset could be explained by a developmental rather than a neurodegenerative disorder. The reason for the lack of response to treatment remains unclear.

The case is unusual but highlights the need to question patients with Möbius syndrome specifically about sleep disturbance and it supports the theory that Möbius syndrome is a variable disorder affecting brainstem development.

Footnotes

Competing interests: None.

References

1. Verzijl H T, van der Zwaag B, Cruysberg J R. et al Mobius syndrome redefined: a syndrome of rhombencephalic maldevelopment. Neurology 2003. 61327–333.333 [PubMed]
2. Schenck C H. Mahowald MW. REM sleep behavior disorder: clinical, developmental, and neuroscience perspectives 16 years after its formal identification, Sleep 2002. 25120–138.138 [PubMed]
3. Mayer G, Blanke J. Moebius syndrome, narcolepsy and parasomnias: Report on two patients. Somnolgie 2004. 8110
4. Parkes J D. Genetic factors in human sleep disorders with special reference to Norrie disease, Prader–Willi syndrome and Moebius syndrome. J Sleep Res 1999. 8(Suppl 1)14–22.22 [PubMed]
5. Plazzi G, Montagna P. Remitting REM sleep behavior disorder as the initial sign of multiple sclerosis. Sleep Med 2002. 3437–439.439 [PubMed]

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