Table 2a.

Allelic Disorders to Consider in the Differential Diagnosis of Apert Syndrome

Allelic DisorderMOIFeatures of Allelic Disorder
In common with "classic" Apert syndromeNot seen in Apert syndrome
FGFR2-related
Antley-Bixler
syndrome 1		AD
  • Craniosynostosis (coronal & lambdoidal)
  • Brachyturricephaly w/frontal bossing
  • Ocular proptosis
  • Downslanting palpebral fissures
  • Radiohumeral synostosis
  • Depression of nasal bridge
  • Low-set, protruding ears
  • Medial bowing of ulnae
  • Bowing of femurs
  • Slender hands & feet
  • Contractures at proximal IP joints
  • Fractures
  • Advanced bone age
  • Congenital heart disease
  • Renal anomalies
  • Abnormalities of female genitalia
  • Signs of congenital adrenal hyperplasia
Beare-
Stevenson
syndrome 2		AD
  • Craniosynostosis (coronal most common)
  • Midface hypoplasia
  • Natal teeth
  • Pyloric stenosis
  • Furrowed palms & soles
  • Widespread cutis gyrata
  • Acanthosis nigricans
  • Skin tags
  • Prominent umbilicus
  • Accessory nipples
  • Bifid scrotum
  • Prominent labial raphe
  • Rugated labia majora
Crouzon syndrome 2AD
  • Craniosynostosis (multisuture, coronal most common)
  • Brachyturricephaly
  • Maxillary hypoplasia
  • Obstructive sleep apnea
  • Tracheal cartilaginous sleeve
  • Hypertelorism
  • Ocular proptosis
  • Papilledema
  • Strabismus
  • Atresia of auditory canals
  • Conductive hearing loss
  • Hydrocephalus
  • Cervical spine fusions
  • Chiari 1 malformation more common
  • Midface retrusion w/less vertical impaction
Jackson-Weiss syndrome 2AD
  • Craniosynostosis (coronal most common)
  • Maxillary hypoplasia
  • Obstructive sleep apnea
  • Hypertelorism
  • Ocular proptosis
  • Strabismus
Radiographic abnormalities of the foot incl:
  • Fusion of tarsal & metatarsal bones
  • 2-3 syndactyly
  • Broad & medially deviated great toes
  • Short 1st metatarsals
  • Broad proximal phalanges
Pfeiffer syndrome types 1, 2, & 3 2AD
  • Craniosynostosis (multisuture, coronal most common)
  • Brachyturricephaly
  • Maxillary hypoplasia
  • Obstructive sleep apnea
  • Tracheal cartilaginous sleeve
  • Hypertelorism
  • Ocular proptosis
  • Papilledema
  • Strabismus
  • Downslanting palpebral fissures
  • Atresia of auditory canals
  • Conductive hearing loss
  • Hydrocephalus
  • Cervical spine fusions
  • Radiohumeral fusions
  • Chiari 1 malformation more common
  • Broad & deviated thumbs & great toes
  • Brachydactyly
FGFR2-related Saethre-Chotzen syndrome 3AD
  • Craniosynostosis (unilateral or bilateral coronal)
  • Brachyturricephaly
  • Maxillary hypoplasia
  • Obstructive sleep apnea
  • High-arched palate
  • Hypertelorism
  • Downslanting palpebral fissures
  • Hearing loss
  • Ptosis
  • Facial asymmetry
  • Low anterior hairline
  • Parietal foramina
  • Characteristic ear (small pinna w/a prominent crus)
  • Partial 2-3 syndactyly of fingers
  • Duplicated distal phalanx of hallux
1.

Antley-Bixler syndrome is caused by mutation of FGFR2 or POR (Note: POR-related Antley-Bixler syndrome is inherited in an autosomal recessive manner.

2.
3.

See Saethre-Chotzen Syndrome. Saethre-Chotzen syndrome is typically caused by mutation of TWIST1, but a family with phenotypic features of Saethre-Chotzen syndrome and normal TWIST1 sequence analysis had an FGFR2 pathogenic variant [Freitas et al 2006].

From: Apert Syndrome

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