Table 3.

Disorders with Facial Weakness and Hypotonia to Consider in the Differential Diagnosis of STAC3 Disorder

DiffDx DisorderGene(s)MOIAdditional Clinical Features of DiffDx Disorder
Overlapping w/STAC3 DisorderDistinguishing from STAC3 Disorder
Central core disease (OMIM 117000) RYR1 AD
AR
  • Respiratory insufficiency
  • Contractures
  • Arthrogryposis
  • Susceptibility to MH
  • External ophthalmoplegia may be present.
  • Serum CK may be ↑ in King-Denborough syndrome.
RYR1-related congenital fiber-type disproportionAR
RYR1-related multiminicore diseaseAR
RYR1-related King-Denborough syndrome 1 (See Malignant Hyperthermia Susceptibility.)AD
Carey Fineman Ziter syndrome 2 (OMIM 254940) MYMK AR
  • Upturned/broad nasal tip
  • Micro/retrognathia
  • Generalized muscle hypoplasia
  • Delayed motor milestones
  • Normal cognition
No susceptibility to MH documented to date
Moebius syndrome 3 (OMIM 157900)Unknown etiology
in most
cases 4
PLXND1
REV3L 5		Unknown
in most
cases;
AD in
small # of
persons 4
  • Cleft palate
  • Talipes equinovarus
  • Short stature
  • Scoliosis
  • Joint contractures
  • Impairment in ocular abduction is obligatory.
  • Variably present:
    • Cranial nerve abnormalities
    • Hearing loss
    • Poland anomaly
    • Limb reduction defects
    • DD, ASD

AD = autosomal dominant; AR = autosomal recessive; ASD = autism spectrum disorder; DD = developmental delay; DiffDx = differential diagnosis; MH = malignant hyperthermia; MOI = mode of inheritance; XL = X-linked

1.
2.
3.

Moebius syndrome was defined by the Moebius Syndrome Foundation Research Conference with the minimum criteria of congenital, nonprogressive facial weakness with limited abduction of one or both eyes [Miller 2007].

4.

Both genetic and environmental etiologies have been proposed. Additionally, prenatal exposure to misoprostol and other agents has been known to cause a Moebius syndrome phenotype.

5.

Heterozygous de novo pathogenic variants in PLXND1 and REV3L have been described in a small number of individuals with congenital facial weakness associated with a variety of additional findings that overlap the Moebius syndrome spectrum [Tomas-Roca et al 2015].

From: STAC3 Disorder

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