FGFR2 Sequencing

Mutations in FGFR2 are associated with various craniosynostosis syndromes including Crouzon syndrome, Apert syndrome, Pfeiffer syndrome, Jackson-Weiss syndrome, Beare-Stevenson syndrome, and FGFR-related isolated coronal synostosis. These conditions are inherited in an autosomal dominant manner. Mutations may be inherited from an affected parent or may be de novo.

Pfeiffer syndrome is divided into three subtypes with type 2 and 3 being more common and severe than type 1, which has a better overall prognosis. Type 1 is characterized by craniosynostosis, midface hypoplasia, broad and medially deviated thumbs and great toes, and varying degrees of brachydactyly. Other findings may include hearing loss and/or hydrocephalus. Intellect is typically normal. Types 2 and 3 have more extreme craniosynostosis, significant proptosis, and broad and medially deviated thumbs and great toes. Other findings may include choanal stenosis/atresia, laryngotracheal abnormalities, hydrocephalus, and seizures. In addition type 2 may have cleft palate. Developmental delay/intellectual disability is common in both.

Pfeiffer syndrome is inherited in an autosomal dominant manner. Mutations may be inherited from an affected parent or may be de novo. Approximately 5% of Pfeiffer syndrome type 1 cases are due to the p.Pro252Arg mutation in the FGFR1 gene, while the remaining 95% of cases are due to sequence variants in the FGFR2 gene. This laboratory performs targeted mutation analysis for the p.Pro252Arg mutation in the FGFR1 gene as well as Sanger sequencing of the FGFR2 gene.

Crouzon syndrome is characterized by craniosynostosis, proptosis, strabismus, and mandibular prognathism. Intellect is typically normal. Extremities are also typically normal although radiographic images may identify metacarpal-phalangeal shortening. A small proportion of individuals may develop hydrocephalus. Crouzon syndrome is due to a mutation in the FGFR2 gene.

Apert syndrome features include craniosynostosis, midface hypoplasia, and soft tissue and bony syndactyly of fingers and toes. Less common findings include rhizomelic shortening, fused cervical vertebrae, hydrocephalus, and cardiac or gastrointestinal defects. Approximately 50% of individuals have varying degrees of developmental delay/intellectual disability. Apert syndrome is due to a mutation in the FGFR2 gene.

Jackson Weiss syndrome is characterized by craniosynostosis, mandibular prognathism, broad and medially deviated great toes with normal hands, abnormally formed tarsals, short first metatarsal, and typically normal intellect. Jackson Weiss syndrome is due to a mutation in the FGFR2 gene.

Beare-Stevenson syndrome features include craniosynostosis, midface hypoplasia, abnormal ears, widespread cutis gyrata and acanthosis nigricans, skin tags, accessory nipples, genital abnormalities, pyloric stenosis, and anterior anus. All individuals have intellectual disability. Beare-Stevenson syndrome is due to a mutation in the FGFR2 gene.

The only feature of FGFR-related isolated coronal synostosis is unilateral coronal craniosynostosis, which is due to a mutation in the FGFR2 gene.

This laboratory performs Sanger sequencing of the FGFR2 gene.

Forms & Docs

Ordering

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Test Code
S0845

Turn Around Time
2-3 weeks

Billing

CPT Code
81479×1

Ordering Guidance

In the case of coronal craniosynostosis and absence of other hallmark features, typically FGFR2 sequencing, FGFR3 Muenke mutation analysis, and TWIST sequencing and deletion/duplication are ordered in combination.

If there are questions regarding this test, please contact Client Services at 617-553-5880 or clientservices@claritasgenomics.com

Details

Genes Covered
FGFR2

Methods
Sanger