Table 2.

Disorders to Consider in the Differential Diagnosis of Ritscher-Schinzel Syndrome

DiffDx DisorderGene(s)MOIClinical Features of DiffDx Disorder
Overlapping w/RSSDistinguishing from RSS
Joubert Syndrome >30 genes 1AR
(XL, digenic) 2
  • ID
  • Hypoplasia of the cerebral vermis
  • Ocular colobomas
  • Polydactyly
  • Retinal dystrophy
  • Cystic kidneys
  • Presence of "molar tooth sign" neuroradiologic finding
Ellis-van Creveld syndrome EVC
EVC2 		AR
  • CHD
  • Dandy-Walker malformation
  • Limb & palate anomalies
  • Polydactyly
  • Short ribs
  • Absence of characteristic RSS facial features
Cornelia de Lange syndrome HDAC8
NIPBL
RAD21
SMC1A
SMC3 		AD 3
XL
  • ID
  • CHD
  • Craniofacial dysmorphisms
  • Distal limb anomalies
  • Absence of cerebellar hypoplasia
  • Characteristic facial features
CHARGE syndrome CHD7 AD 3
  • ID
  • Dysmorphic facial features
  • Coloboma
  • Palate anomalies
  • CHD
  • Choanal atresia
  • Inner-ear dysgenesis
  • Facial nerve palsies
  • Pituitary dysfunction
  • Absence of characteristic RSS facial features
Kabuki syndrome KDM6A
KMT2D 		AD
XL 4
  • ID
  • Coloboma
  • Palate anomalies
  • Dysmorphic craniofacial features
  • Characteristic facial features
  • Persistence of fetal fingertip pads
Frontonasal dysplasia
(OMIM PS136760)		 ALX1
ALX3
ALX4 		AR
  • ID
  • Dysmorphic craniofacial features
  • Hypertelorism
  • Palate anomalies
  • Distal limb anomalies
  • Encephalocele
  • Nasal clefting
  • Distinctive craniofacial features
RSS-like syndrome 5 VPS35L AR
  • ID
  • Dysmorphic craniofacial features
  • CHD
  • Coloboma
  • Cerebellar vermis hypoplasia
  • Severe growth restriction
  • Microphthalmia
  • Periventricular nodular heterotopia
  • Chondrodysplasia punctata
  • Mesomelia of upper extremities
Loucks-Innes syndrome 6 DPH1 AR
  • ID
  • Short stature
  • Dandy-Walker malformation, cerebellar vermis hypoplasia, & posterior fossa cyst
  • CHD
  • Renal anomalies
  • Distinctive craniofacial features
  • Ectodermal findings

AD = autosomal dominant; AR = autosomal recessive; CHD = congenital heart defect; DiffDx = differential diagnosis; ID = intellectual disability; MOI = mode of inheritance; RSS = Ritscher-Schinzel syndrome; XL = X-linked

1.
2.

Joubert syndrome is predominantly inherited in an autosomal recessive manner. Joubert syndrome caused by pathogenic variants in OFD1 is inherited in an X-linked manner. Digenic inheritance has been reported.

3.

Typically caused by a de novo pathogenic variant

4.

The proportion of Kabuki syndrome caused by de novo variants is unknown, but is likely high based on clinical experience.

5.
6.

From: Ritscher-Schinzel Syndrome

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