Development of a Strain of Rabbits with Congenital Simple Nonsyndromic Coronal Suture Synostosis Part II: Somatic and Craniofacial Growth Patterns

Abstract

In the March 1993 issue of The Cleft Palate-Craniofacial Journal we reported a female rabbit born in our laboratory with complete bilateral coronal suture (CS) synostosis. This follow-up study presents our attempts to breed the animal and establish a strain of craniosynostotic rabbits. The second part of this study presents longitudinal somatic and craniofacial growth data in offspring with coronal suture synostosis. Serial growth data from 72 animals were collected for the present study. The sample consisted of 11 animals (10 offspring and the original female) with complete nonsyndromic unilateral (plagiocephalic) or bilateral (brachycephalic) CS synostosis, 19 animals with partial CS synostosis, and 42 unaffected control litter mates. At 10 days of age, all animals had radiopaque amalgam markers placed on either side of the frontonasal, coronal, anterior lambdoidal, and sagittal sutures. Body weights and serial lateral and dorsoventral head radiographs were taken at 1.5 (10 days), 6, 12, and 18 weeks of age. All animals showed similar body weights at 1.5 weeks of age, while completely synostosed animals exhibited a slight (about 12%), but significantly (p < .001) lowered body weight by 18 weeks of age. Results revealed that by 1.5 weeks of age the completely synostosed animals already exhibited brachycephalic cranial vaults, midfacial hypoplasia, and increased flattening of the cranial base compared to unaffected siblings. This pattern continued through 18 weeks of age, with the partially synostosed animals exhibiting intermediate morphologies.(ABSTRACT TRUNCATED AT 250 WORDS)

Rescue of coronal suture fusion using transforming growth factor‐beta 3 (Tgf‐β3) in rabbits with delayed‐onset craniosynostosis

“…Although the pathogenesis of delayed-onset synostosis is unknown, dense collagen bundles, small bony bridges, and an increased number of sutural bones have all been observed in the coronal sutures of rabbits with delayed-onset synostosis (Mooney et al, 1994a(Mooney et al, ,b, 1996aBurrows et al, 1995Burrows et al, , 1997Losken et al, 1998Losken et al, , 1999. These bundles, bridges, and supernumerary bones probably immobilize the suture and result in neurocranial growth restrictions and altered neurocapsular growth vectors, as observed in both the rabbit model (Mooney et al, 1994b;Burrows et al, 1995;Losken et al, 1998) and clinically (Reddy et al, 1990;Hoffman and Reddy, 1991;Cohen et al, 1993;Cohen and MacLean, 2000). The partially immobilized coronal sutures in rabbits from our colony usually synostose at 42-84 days of age (normal suture fusion in rabbits occurs at about 3-4 years of age (Persson et al, 1978)), as observed histologically in sham control rabbits in the present study and in previous investigations (Mooney et al, 1994b(Mooney et al, , 2002bBurrows et al, 1995;Losken et al, 1998Losken et al, , 1999.…”

“…1) at 10 days of age and the quantitative assessment of coronal suture growth from serial radiographs (Mooney et al, 1994b(Mooney et al, , 1996aBurrows et al, 1995;Losken et al, 1998Losken et al, , 1999. Cephalographs of the rabbits were taken at 10 and 25 days of age, and rabbits in which coronal suture marker separation fell below the 95% confidence interval of the mean for unaffected rabbits were classified as having delayed-onset synostosis.…”

“…Longitudinal body weight and coronal suture growth data were obtained from all rabbits at 10, 25, 42, and 84 days of age (at this age, approximately 80 -90% of calvarial and brain growth is completed in the rabbit) (Harel et al, 1972;Masoud et al, 1986;Mooney et al, 1994b;Burrows et al, 1995).…”

“…Serial lateral and dorsoventral head radiographs were taken with the rabbits tranquilized with an IM injection (0.40 ml/kg) of a solution of 9l% Ketaset (ketamine hydrochloride, 100 mg/ ml; Aveco Co. Inc., Fort Dodge, IA) and 9% Rompun (xy- lazine, 20 mg/ml; Mobay Corp., Shawnee, KS). The heads were immobilized in a specially designed cephalostat, and a Philips Oralix 70 dental x-ray unit (Shelton, CT) was used at an exposure of 50kV, 7mA, with a .17-.50-sec exposure time, and a tube-to-cassette distance held constant at 152 cm (Mooney et al, 1994b;Burrows et al, 1995;Losken et al, 1998Losken et al, , 1999. The radiographs were viewed on a light box, and the amalgam markers at the coronal suture were identified and traced on acetate tracing paper (Figs.…”

“…Premature coronal suture synostosis is associated with secondary deformities in the cranial vault and cranial base (Babler and Persing, 1982;Vannier, 1985, 1986;Burdi et al, 1986;Babler, 1989;Hoyte, 1989;Mooney et al, 1994b;Burrows et al, 1995;Smith et al, 1996), significantly elevated intracranial pressure (Renier, 1989;Gault et al, 1992;Mooney et al, 1998aMooney et al, , 1999Fellows-Mayle et al, 2000), and altered intracranial volume (Singhal et al, 1997;Hudgins et al, 1998;Mooney et al, 1998a,b;Camfield et al, 2000). These conditions may result in optic nerve compression and papilledema, and, if left uncorrected, optic atrophy, blindness (Miller, 2000), cognitive disabilities, and mental retardation (Kapp-Simmonds et al, 1993;Arnaud et al, 1995;Camfield et al, 2000;Persing and Jane, 2000).…”