J Genet Med.  2016 Jun;13(1):31-35. 10.5734/JGM.2016.13.1.31.

Two cases of Antley-Bixler syndrome caused by mutations in different genes, FGFR2 and POR

• Woo H
• Ko JM
• Shin CH
• Yang SW

• KMID: 2327700
• DOI: http://doi.org/10.5734/JGM.2016.13.1.31

Abstract

Antley-Bixler syndrome (ABS) is a rare form of syndromic craniosynostosis with additional systemic synostosis, including radiohumeral or radioulnar synostosis. Another characteristic feature of ABS is mid-facial hypoplasia that leads to airway narrowing after birth. ABS is associated with mutations in the FGFR2 and POR genes. Patients with POR mutations present with either skeletal manifestations or congenital adrenal hyperplasia with ambiguous genitalia. We report here two cases of ABS caused by mutations in FGFR2 and POR. Although the patients had craniosynostosis and radiohumeral synostosis in common and cranioplasty was performed in both cases, the male with POR mutations showed an elevated level of 17α-hydroxyprogesterone during newborn screening and was diagnosed with congenital adrenal hyperplasia by adrenocorticotropic hormone stimulation. This patient has been treated with hydrocortisone and fludrocortisone. He had no ambiguous genitalia but had bilateral cryptorchidism. On the other hand, the female with the FGFR2 mutation showed severe clinical manifestations: upper airway narrowing leading to tracheostomy, kyphosis of the cervical spine, and coccyx deformity. ABS shows locus heterogeneity, and mutations in two different genes can cause similar craniofacial and skeletal phenotypes. Because the long-term outcomes and inheritance patterns of the disease differ markedly, depending on the causative mutation, early molecular genetic testing is helpful.

Keyword

Antley-Bixler syndrome phenotype; Craniosynostoses; Congenital adrenal hyperplasia; FGFR2; POR

MeSH Terms

Adrenal Hyperplasia, Congenital
Adrenocorticotropic Hormone
Antley-Bixler Syndrome Phenotype*
Coccyx
Congenital Abnormalities
Craniosynostoses
Cryptorchidism
Disorders of Sex Development
Female
Fludrocortisone
Hand
Humans
Hydrocortisone
Infant, Newborn
Inheritance Patterns
Kyphosis
Male
Mass Screening
Molecular Biology
Parturition
Phenotype
Population Characteristics
Spine
Synostosis
Tracheostomy
Adrenocorticotropic Hormone
Fludrocortisone
Hydrocortisone