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Lyulcheva-Bennett et al. J Transl Genet Genom 2023;7:259-73 https://dx.doi.org/10.20517/jtgg.2023.33 Page 263

Table 1. Proposed diagnostic criteria for MBS utilising a combination of essential and supporting features to facilitate standardised
MBS diagnosis and reporting
Diagnosis Criteria Supporting features
Typical MBS Essential features: Neurological:
•Bilateral congenital, non-progressive CNVI palsy •Involvement of other cranial nerves
•Bilateral congenital, non-progressive CNVII palsy •Hypotonia
•Presence of a full vertical gaze •Dysarthria
•Abnormal motor coordination
Presence of all three essential features (bilateral or unilateral) •Brain imaging abnormalities (e.g., volumetric reduction in
plus ≥ 2 supporting features in the absence of chromosome key brainstem areas)
abnormalities Musculoskeletal:

•Lower limb anomalies (e.g., talipes)
•Upper limb anomalies (e.g., Poland anomaly,
symbrachydactyly)

Craniofacial:
Isolated MBS Presence of all three essential features (bilateral or unilateral) •Craniofacial dysmorphism (e.g., low set/dysplastic ears,
plus ≤ 1 supporting features in the absence of chromosome hypertelorism, epicanthic folds)
abnormalities •High or cleft palate
•Micrognathia
•Hypoplastic/atrophic tongue

Gastrointestinal/Nutritional:
•Swallowing/feeding difficulties
•Failure to thrive
Cardiovascular:
•Cardiac anomalies (e.g., dextrocardia, atrial/ventricular
septal defects, transposition of the great vessels)
Developmental:
•Developmental delay
•Sleep problems
•Behavioural and/or social communication difficulties
Alternative •Presence of only two essential features with or without supporting features
diagnosis likely ·Presence of three essential features and one of: atypical additional features, such as profound intellectual disability or
atypical dysmorphic features
·Family history

Based on our centre’s recent experience of 42 MBS patients, where 97% of MBS patients meet the diagnostic criteria for “Typical MBS” (n = 37)
of all essential MBS features and ≥ 2 supporting features in the absence of chromosome abnormalities. 84% (n = 32) of our cohort presented with
the essential features and ≥ 3 supporting features.

Figure 2. Two subgroups of MBS. Clinical features of MBS cluster to form two subgroups of MBS. Type 1 MBS tends to exhibit limb
abnormalities, micrognathia, and swallowing difficulties. Nearly two-thirds of patients exhibiting any one of the marked features (*) had
all three of those features. Type 2 MBS is more likely to include developmental delay, additional cranial nerve palsies, and palatal and
brain imaging abnormalities, but the clustering is weaker.