Craniosynostosis Syndromes Flashcards
What percentage of craniosynostosis is syndromic?
15–30%
What is the mechanism in FGFR2-related disorders?
Mutations in the FGFR2 gene are thought to result in production of an FGFR2 protein with overactive
signaling, which causes the bones of the skull to fuse prematurely
Which suture is most commonly affected in craniosynostoses?
The sagittal suture (40–55%) is the most commonly affected, followed by the coronal (20–25%), metopic
(5–15%), and lambdoid (<5%) sutures.
What are the most common additional features seen with craniosynostoses?
Ocular hypertelorism
proptosis (eye-bulging)
beaking of the nose
midface hypoplasia
What is the prevalence of craniosynostosis?
Estimated to be 1 in 2100 to 2500 live births
In what disorders do you see a cloverleaf skull?
More commonly associated with thanatophoric dysplasia,
achondrogensis, campomelic dysplasia
What gene is associated with Apert syndrome?
FGFR2 (AD)
Some association with paternal age
What are the characteristics of Apert syndrome?
Severe symmetrical syndactyly – distinguishes it from
other FGFR2-relaterd syndromes (often 2nd,3rd and 4th
digits)
- Craniosynostosis (coronal synostosis)
- Flat forehead
- Retracted midface, airway obstruction
- Proptosis, hypertelorism
- Skeletal anomalies such as poor joint mobility, cleft palate,
orthodontic problems, short stature - GI such as malrotation, esophageal anomalies
- Learning disabilities
What is the genetic cause of Crouzon syndrome?
FGFR2 (AD)
-Mutations in ERF have been associated with a Crouzon-like syndrome
What are the characteristics of Crouzon syndrome?
- Midface hypoplasia
- Prominent nasal bridge
- Proptosis, strabismus
- Underdeveloped upper jaw, protrusion of lower jaw, overcrowded teeth
- Hearing loss
- Most have normal intelligence
- Airway blockages leading to breathing and respiratory difficulties
- Usually no intellectual impairment or effects of the arms, legs or hands
What is Crouzon with Acanthosis Nigricans?
- Very similar to Crouzon syndrome
Differences
* CWAN has acanthosis nigricans (pigmentary changes in the skin fold regions)
* In CWAN hearing loss is less common
* CWAN has normal hands and feet
* “Typically” normal in Crouzon
* Vertebral fusions in 25% (often C2-C3) seen in Crouzon
What is the genetic cause of Antley-Bixler syndrome?
FGFR2 (AD)
- Mostly de novo (w/out genital anomalies and disordered steriodogenesis)
POR (AR)
- With with genital anomalies and disordered steroidogenesis
What are the characteristics of Antley-Bixler syndrome?
- Midface hypoplasia
- Choanal atresia or stenosis
- Multiple joint contractures, arachnodactyly
- High mortality due to airway compromise
- With POR mutations, also see genital anomalies and abnormal steroidogenesis
- May be at risk for adrenal insufficiency and Addisonian crisis with illness or surgery
- High doses of fluconazole can cause similar features
What is the genetic cause of Beare-Stevenson cutis gyrata
syndrome?
FGFR2 (AD)
What are the features of Beare-Stevenson cutis gyrata
syndrome?
- Multisuture craniosynostosis with cloverleaf skull
- Moderate-to-severe midface retrusion, proptosis, abnormal ears, cleft palate, conductive hearing loss, natal teeth, and relative prognathism (protruding jaw)
- Multilevel airway obstruction includes choanal stenosis, tongue-based airway obstruction, and tracheal anomalies, with survivors requiring endotracheal intubation with mechanical ventilation and/or tracheostomy
- Neonatal mortality is common
- Hands and feet are normal aside from cutis gyrata
- Intellectual disability is present in all affected individuals
- Widespread cutis gyrata and acanthosis nigricans are usually evident at birth
- Also hirsutism, skin tags, prominent umbilicus with redundant tissue, and accessory nipples are also seen.
- Genitourinary anomalies (e.g., bifid scrotum, prominent labial raphe, rugated labia majora), pyloric stenosis, and anterior anus)
