An X-linked syndrome, strangely more severe in
females, combining frontonasal dysplasia, coronal craniosynostosis, various other skeletal and soft tissue
abnormalities and mild mental deficiency.
Facial asymmetry, hypertelorism, bifid nose, repaired cleft lip, and short neck in a
3-year-old girl with craniofrontonasal dysplasia.
Incidence is not known. Females
are affected approximately four to six times more often than males, with the
disease being usually much more severe in females, a highly unusual feature
for an X-linked (dominant) disorder. The mutation has been mapped to Xp22.
Almost all symptoms (except the urogenital
findings) are either only present in females or more severe in females.
Multiple malformations have been described involving the head and neck
(coronal synostosis, anterior bifid cranium, brachycephaly, frontal bossing,
facial asymmetry [often secondary to unicoronal craniosynostosis],
downslanting palpebral fissures, hypertelorism, strabismus, nystagmus, bifid
nose, high arched palate, cleft lip, cleft palate, short neck), the chest
(diaphragmatic hernia, Sprengel deformity, clavicular pseudarthrosis, pectus
excavatus, axillary pterygia, unilateral breast hypoplasia), and the
skeleton (growth retardation, scoliosis, muscular hypotonia and joint
laxity, limb abnormalities such as different leg length, brachydactyly,
syndactyly of fingers and toes, broad halluces). Other features can include
developmental delay, dry, thick, frizzy hair, longitudinally grooved nails,
shawl scrotum, and hypospadias.
Airway management difficulties should be
expected depending on the degree of asymmetry and palatal anomalies.
Maintenance of spontaneous ventilation is recommended until the airway has
been secured. Intraoperative positioning may be difficult and requires care.
The subclavian approach for central venous cannulation may be difficult in
the presence of clavicular pseudarthrosis. Be aware of the possibility of
diaphragmatic hernias in newborns. Mental retardation and deafness may affect patient
cooperation. Sedative and/or anxiolytic premedication and/or the presence of
the primary caregiver during induction of anesthesia may be helpful.
Pulleyn LJ, Winter RM, Reardon W, et al: Further evidence from two families
that craniofrontonasal dysplasia maps to Xp22. Clin Genet
Saavedra D, Richieri-Costa A, Guion-Almeida ML, et al: Craniofrontonasal
syndrome: Study of 41 patients. Am J Med Genet
Wieacker P, Wieland I: Clinical and genetic aspects of craniofrontonasal syndrome: towards resolving a genetic
paradox. Mol Genet Metab