CRANIOSYNOSTOSES

Question 1

ANTLEY-BIXLER SYN (PART OF CYTOCHROME P450 OXIDOREDUCTASE DEFICIENCY SPECTRUM)

Answer 1

*Craniosynostosis, *midfacial hypoplasia, frontal bossing, of forehead, *radiohumeral synostosis, *ambiguous genitalia (females = masculinized vs males = undermasculinized); Teratogen exposure to fluconazole; Genetics: Type 1 POR (A recessive), Type 2 (FGFR2); Testing Strategy: FGFR2 NGS or POR» urine steroid profile; POR-related ABS may be flagged as pos screen for CAH on NBS

Question 2

APERT SYN

Answer 2

Multisuture craniosynostosis (coronal in all), midface hyoplasia and retrusion, fusion of middle three digits of hand (syndactyly); Genetics: de novo FGFR2 mutations; Advanced Paternal Age; Testing Strategy: Two pathogenic mutations common in FGFR2

Question 3

PFEIFFER SYN

Answer 3

Major overlap with Crouzon; Multisuture craniosynostosis, midface retrusion (more vertical impaction compared to Crouzon), conductive hearing loss, *broad medially dviated thumbs and great toes; Genetics: FGFR2 gene (FGFR1 about 5% type 1); Testing strategy: NGS of FGFR2

Question 4

CROUZON SYN

Answer 4

Multisuture craniosynostosis (variable), *craniofeatures more prominent with age (midface retrusion and proptosis), typically normal hands and feet; vertebral fusions in about 25% (cervical); Genetics: FGFR2 gene; if w/aconthosis nigricans&raquo_space; Single FGFR3 mutation

Question 5

JACKSON-WEISS SYN

Answer 5

Multisuture craniosynostosis, proptosis and prognathism, normal hands but broad medially deviated great toes, knock knees (genu valgum); Genetics: FGFR2 gene

Question 6

MUENKE SYN (MOST COMMON CRANIOSYNOSTOSIS SYNDROME)

Answer 6

Highly variable phenotype–uni- or bicoronal craniosynostosis, *carpal and tarsal fusions are diagnostic but not always present, sensorineural hearing loss, neurological problems including DD and seizures; Genetics: FGFR3–one specific mutation; however best to full sequence FGFR3 given overlap with other craniosynostosis syndromes

Question 7

SAETHRE-CHOTZEN SYN

Answer 7

Coronal synostosis, facial asymmetry, characteristic ear; Genetics: TWIST1 gene; Testing Strategy: if w/ DD, CMA first; Many have an affected parent (incomplete penetrance and variable expressivity)