Inherited syndrome with craniofacial dysmorphism and
skeletal and other anomalies. Frequently associated with respiratory failure
in the neonatal period.
Multisynostotic Osteodysgenesis with Long Bone Fractures;
First description in 1975 by Ray M. Antley and David
Bixler, two American physicians.
Inherited as an autosomal recessive genetic
trait. A few cases may be sporadic or transmitted as an autosomal dominant
trait. Parental consanguinity is a known risk factor.
The flavoprotein POR (cytochrome P-450
[oxido]reductase) is the electron donator for all microsomal P-450 enzymes.
Mutations in this POR gene could be demonstrated in patients with
Antley-Bixler syndrome. The lack or malfunction of POR may result in
accumulation of drugs and environmental toxins usually metabolized by
hepatic cytochrome P-450, which may result in levels high enough to cause
teratogenicity. Fluconazole is one drug that has been implicated in the
pathogenesis of Antley-Bixler syndrome. This genetic defect has been mapped
to 7q.11.2. The role of a mutation in the FGF-2 gene, which initially was
suspected to be the cause of this disorder, now seems less certain.
Abnormalities of the steroid biogenesis have been reported and seem to be at
least partly responsible for the genital anomalies found in female patients.
Based on clinical findings of trapezoidocephaly and
multiple skeletal fusion. Craniofacial anomalies result in severe upper
airway obstruction that can lead to death secondary to respiratory failure
at birth or in the first weeks of life in approximately 50% of cases.
Multiple malformations predominately involve the
head: severe midface hypoplasia, frontal bossing, craniosynostosis,
brachycephaly, low-set dysplastic ears, small nose with low nasal bridge,
anteverted nares, and choanal atresia are common. Acrocephaly, flat
supraorbital ridges, proptosis, down-slanted palpebral fissures,
hypertelorism, paresis of ocular muscles, cleft soft palate with bifid
uvula, microstoma, and long philtrum are less common findings. Skeletal
findings include narrowing of the rib cage, abnormal vertebrae, pelvic
anomalies (narrow iliac wings), absent or abnormal (bowing) femora,
radioulnar and radiohumeral synostosis, restricted joint mobility secondary
to contractures, camptodactyly, arachnodactyly, talipes varus or valgus, and
multiple fractures. Congenital fractures (in some cases multiple) have been
described. Congenital cardiac defects (e.g., atrial septal defect),
anomalies of the urinary tract (renal agenesis) and external female
genitalia (vaginal atresia, hypoplastic labia majora, agglutinated labia
minora), and imperforate anus may occur. Intellectual status can be normal,
but variable degrees of mental retardation and hydrocephalus have been
Evaluate the airway carefully
(clinically, radiographically, eventually use fiberoptic examination). Check
overall joint mobility (particularly neck mobility and mouth opening).
Determine neurologic status and rule out cardiac anomalies (clinically,
echocardiographically, electrocardiographically). Check renal function
Airway management (mask ventilation,
direct laryngoscopy, tracheal intubation) can be difficult because of facial
malformations, as reflected by high mortality in the first weeks of life
secondary to respiratory complications. Choanal atresia may require
emergency tracheostomy at birth. Maintenance of spontaneous ventilation and ...