Table 2.

Disorders to Consider in the Differential Diagnosis of Saethre-Chotzen Syndrome (SCS)

DisorderGene(s)MOIClinical FeaturesComment
OverlappingDistinguishing
Muenke syndrome FGFR3 1ADUnilateral/bilateral coronal synostosisIn SCS: 2
  • Low-set frontal hairline
  • Downward-sloping palpebral fissures
  • Ptosis
  • Ear abnormalities
  • Interdigital webbing

In Muenke syndrome:

  • Higher prevalence of DD (35%, vs 5% in SCS)
  • SNHL (34%, vs rare in SCS)
Consider testing for FGFR3 p.Pro250Arg if a TWIST1 pathogenic variant is not identified in a person w/a presumed diagnosis of SCS.
Isolated unilateral
coronal
synostosis (IUCS) 3, 4
(OMIM PS123100)		 ALX4
ERF
MSX2
SMAD6
TCF12
TWIST1
ZIC1 		ADIf left untreated or incompletely treated, IUCS can → facial asymmetry resembling SCS.By definition, IUCS is not assoc w/other clinical findings of SCS.
  • Coronal synostosis is 2nd most common form of single-suture fusion (after sagittal synostosis).
  • Isolated coronal fusion is ~10x more common than SCS.
Baller-Gerold syndrome (BGS) RECQL4 ARBilateral coronal craniosynostosis → brachycephaly w/ocular proptosis & flat foreheadIn BGS:
  • Radial ray defect, usually w/oligodactyly (↓ # of digits), aplasia or hypoplasia of the thumb, &/or aplasia or hypoplasia of the radius
  • Growth restriction
  • Poikiloderma
Rothmund-Thomson syndrome & RAPADILINO syndrome (OMIM 266280), also caused by RECQL4 pathogenic variants, have overlapping clinical features w/BGS.

AD = autosomal dominant; AR = autosomal recessive; DD = developmental delay; MOI = mode of inheritance; SNHL = sensorineural hearing loss

1.

Muenke syndrome is defined by the presence of the specific FGFR3 pathogenic variant c.749C>G, which results in the protein change p.Pro250Arg.

2.

In their study of 39 families (71 affected individuals) ascertained on the basis of coronal synostosis, Kress et al [2006] determined that individuals with a TWIST1 pathogenic variant could be distinguished from those with the FGFR3 p.Pro250Arg pathogenic variant based on differences in facial features.

3.

Isolated coronal synostosis refers to coronal suture fusion with no evidence of other malformations.

4.

In an analysis of 186 individuals with isolated single-suture craniosynostosis, 7.5% had at least one rare deletion or duplication found using CMA [Mefford et al 2010].

From: Saethre-Chotzen Syndrome

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