Page 30 - Read Online

Lyulcheva-Bennett et al. J Transl Genet Genom 2023;7:259-73 https://dx.doi.org/10.20517/jtgg.2023.33 Page 261

CLINICAL FEATURES OF MBS
Moebius Syndrome (MBS) is a complex neurodevelopmental disorder with a spectrum of clinical
[5]
manifestations . At its core, MBS is characterised by congenital, non-progressive facial weakness and
limited abduction of one or both eyes . The diagnostic criteria have evolved over time, with the current
[3]
minimum being congenital, non-progressive, bilateral or unilateral, symmetrical or asymmetrical cranial
nerve VI (CNVI), and CNVII palsies, accompanied by a full vertical gaze [8,12] .

The hallmark clinical features of MBS stem from CN VI and VII dysfunction, leading to the distinctive loss
of facial expression and compromised ocular motility. However, the syndrome’s clinical landscape is vast
and often extends beyond these primary manifestations [Figure 1]. Other cranial neuropathies,
[5]
particularly involving CN V, IX, X, and XII, have been documented [9,13] . These result in oro-motor disorders,
manifesting as impaired sucking and swallowing, which can lead to failure to thrive in infancy and
dysphagia [3,14] . Feeding difficulties in infants with MBS are further exacerbated by the presence of a high-
arched or cleft palate, observed in approximately 70% of patients . Speech delay, dysarthria, poor
[5]
intelligibility, and other speech problems are frequently encountered in MBS, further complicating the
clinical picture [3,9,14] . Historically, children with MBS were believed to have a much higher prevalence of
autism and autistic-like behaviours compared to the general population . However, the exact prevalence is
[4]
not clear due to the known challenges of making a diagnosis of autism in the context of impaired social and
communication skills secondary to a physical/structural condition, such as MBS.

Sleep disturbances are a notable concern in Moebius Syndrome, with approximately one-third of affected
children experiencing sleep-related challenges . These disturbances are believed to arise from the
[8]
[15]
maldevelopment of the rhombencephalon with the reticular formation, which is involved in the sleep-
wake cycle, in close proximity to the area of the brainstem affected by MBS . Manifestations include night
[15]
terrors, sleepwalking, and recurrent awakenings with subsequent difficulties in resuming sleep. Such sleep
disruptions not only impact the child but also pose a significant strain on their families. For some
individuals with MBS, these sleep issues can persist, extending into their adult years and necessitating
ongoing management and support .
[5,8]

The syndrome’s diverse clinical features also encompass lingual hypoplasia, sensorineural hearing loss, and
craniofacial dysmorphisms such as epicanthic folds, micrognathia, and dysplastic or low-set ears [13,16] . Limb
abnormalities, including syndactyly, pes planus, and talipes, are not uncommon [13,16] . Notably, over a third of
[5]
MBS patients exhibit an association with Poland anomaly . Cardiac anomalies, such as dextrocardia, atrial
or ventricular septal defects, and transposition of the great vessels, further complicate the clinical
picture [5,17] . While the majority of MBS patients possess normal cognitive abilities, about 10% may
experience varying degrees of intellectual disability . Developmental delays and motor coordination
[16]
challenges are frequently associated with MBS . Neuroimaging often reveals abnormalities consistent with
[5]
the clinical symptoms of CN VI and VII dysfunction, including an absent facial colliculus and pontine
hypoplasia . Additionally, lower brainstem hypoplasia has been linked to the occasional primary
[18]
respiratory dysfunction observed in MBS cases .
[16]
The physical manifestations, coupled with the psychosocial challenges stemming from facial paralysis and
other symptoms, can significantly impact the quality of life of affected individuals. This underscores the
importance of a comprehensive approach to care, addressing both the medical and emotional needs of MBS
patients [3,14,19] .