Analysis Tools
mortality/aging
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• all homozygotes die shortly after birth
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• at birth, homozygotes are obtained at non-Mendelian ratios, suggesting embryonic lethality
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behavior/neurological
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• newborn homozygotes lack milk in their stomachs
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growth/size/body
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• extensive chondroid bone develops along the incisive alveolar bone at the tips of the dentary
• the incisivium is broader and shorter than normal
• both sets of incisors are shorter and malformed
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• the molar alveolae are shorter, broader and deeper
• the alveolar openings are constricted distally and broadened proximally
• the buccal molar walls are weaker and ventrally reflected
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• the mandicular and maxillary molars display malformed and poorly mineralized crowns
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• the mandicular and maxillary molars display malformed and poorly mineralized crowns
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• a short and abnormal dentary develops around Meckel's cartilage
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• the condylar and angular processes are shorterned, malformed and juxtaposed
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• the condylar and angular processes are shorterned, malformed and juxtaposed
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• the proximal lamina of the coronoid is absent
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• in most cases, the maxillae are dysmorphic
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• in most cases, the premaxillae are dysmorphic
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• in most cases
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small maxilla
(
J:56559
)
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• in most cases
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micrognathia
(
J:56559
)
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• newborns exhibit micrognathia
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• in most cases, lacrimal bones are small and dysmorphic
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• in most cases
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• in most cases, nasal bones are dysmorphic
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• in most cases
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• in most cases, the tectum nasi, solum and paries nasi prominences and associated turbinates are hypoplastic
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• in most cases, the vomer bones are small and dysmorphic
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• newborns display reduced nasal capsular breadth, with chondrocranial and dermatocranial defects in and around the nasal capsule and mesethmoid
• in severe cases, newborns show a symmetric near aplasia of the capsule and mesethmoid
• small, cartilaginous spicules are the only remnants of the side walls of the nasal capsule
• in less severe cases, cartilages in the floor of the nasal capsule are hypoplastic and often associated with a rudimentary vomeronasal organ
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• the medial pterygoid is hypertrophic; its insertion groove is occluded by a broad origin for an abnormal mylohyoid
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• 88% of newborns exhibit primary and secondary palates with variable degrees of clefting
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• 88% of newborns exhibit primary and secondary palates with variable degrees of clefting
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• the right side of the rostral tongue is hypertrophied ventrally
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• the course of the lingual duct and the fascicle pattern of the intrinsic tongue musculature is variably affected
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• in severe cases, the posterior nasal capsule and mesethmoid are reduced, with no evidence of a developing nasal epithelium, true tectum or solum
• in less severe cases, rudimentary branches of the nasal epithelium are present
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• in severe cases, paraseptal cartilages and the vomeronasal organ fail to deveop
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• in most cases (intermediate severity), the trabecular plate-nasal septum deviates to the right; no foramina cribrosa are found on the right and very few on the left
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• in severe cases, a dorsoventrally expanded nasal septum fails to develop (i.e. shortened dorsoventrally)
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• newborns exhibit malformed auditory pinnae
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• the external acoustic meatus is shorter and the tubal cartilage develops in nodules
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• tubal cartilage develops in nodules
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• newborn homozygotes are slightly smaller than wild-type littermates
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craniofacial
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• newborns exhibit variable abnormalities in all cranial bones
• only a few abnormalities are detected in post-cranial axial and appendicular skeleton
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• at E13.5 and E15.5, Meckel's cartilage is shorter and its proximal shaft is severely dysmorphic; the MC orientation deviates twice
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• at E13.5 and E15.5, Meckel's cartilage is shorter than normal
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• all non-exencephalic newborns have calvarial roofs (calottes) with small, hypomineralized parietal and interparietal bones
• in contrast, frontals appear to exhibit normal mineralization
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• all non-exencephalic newborns display small, hypomineralized interparietal bones
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• all non-exencephalic newborns display thicker occipital arch cartilages that expand rostrocaudally
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• all non-exencephalic newborns display small supraoccipital bones with a reduced degree of hypomineralization
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• all non-exencephalic newborns display small, hypomineralized parietal bones
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• alisphenoid bones are slightly dysmorphic
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• the pterygoids have an abnormal amount of chondroid bone and secondary cartilage
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• squamosal bones are slightly dysmorphic
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• extensive chondroid bone develops along the incisive alveolar bone at the tips of the dentary
• the incisivium is broader and shorter than normal
• both sets of incisors are shorter and malformed
|
|
• the molar alveolae are shorter, broader and deeper
• the alveolar openings are constricted distally and broadened proximally
• the buccal molar walls are weaker and ventrally reflected
|
|
• the mandicular and maxillary molars display malformed and poorly mineralized crowns
|
|
• the mandicular and maxillary molars display malformed and poorly mineralized crowns
|
|
• a short and abnormal dentary develops around Meckel's cartilage
|
|
• the condylar and angular processes are shorterned, malformed and juxtaposed
|
|
• the condylar and angular processes are shorterned, malformed and juxtaposed
|
|
• the proximal lamina of the coronoid is absent
|
|
• in most cases, the maxillae are dysmorphic
|
|
• in most cases, the premaxillae are dysmorphic
|
|
• in most cases
|
small maxilla
(
J:56559
)
|
• in most cases
|
micrognathia
(
J:56559
)
|
• newborns exhibit micrognathia
|
|
• in most cases, lacrimal bones are small and dysmorphic
|
|
• in most cases
|
|
• in most cases, nasal bones are dysmorphic
|
|
• in most cases
|
|
• in most cases, the tectum nasi, solum and paries nasi prominences and associated turbinates are hypoplastic
|
|
• in most cases, the vomer bones are small and dysmorphic
|
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• in 88% of homozygotes, ectopic membrane bones (parapalatines) develop caudal to the palatine shelves and rostral to the dysmorphic pterygoids
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• the malleus is caudally extended and thickened at the level of the manumbrium
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• the malleus has a smaller than normal processus brevis
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• at E10.5, frontonasal prominences are hypoplastic
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• at E12.5, the lateral frontonasal prominence is severely reduced
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• newborns display reduced nasal capsular breadth, with chondrocranial and dermatocranial defects in and around the nasal capsule and mesethmoid
• in severe cases, newborns show a symmetric near aplasia of the capsule and mesethmoid
• small, cartilaginous spicules are the only remnants of the side walls of the nasal capsule
• in less severe cases, cartilages in the floor of the nasal capsule are hypoplastic and often associated with a rudimentary vomeronasal organ
|
|
• the medial pterygoid is hypertrophic; its insertion groove is occluded by a broad origin for an abnormal mylohyoid
|
|
• 88% of newborns exhibit primary and secondary palates with variable degrees of clefting
|
|
• 88% of newborns exhibit primary and secondary palates with variable degrees of clefting
|
|
• the right side of the rostral tongue is hypertrophied ventrally
|
|
• the course of the lingual duct and the fascicle pattern of the intrinsic tongue musculature is variably affected
|
|
• in severe cases, the posterior nasal capsule and mesethmoid are reduced, with no evidence of a developing nasal epithelium, true tectum or solum
• in less severe cases, rudimentary branches of the nasal epithelium are present
|
|
• in severe cases, paraseptal cartilages and the vomeronasal organ fail to deveop
|
|
• in most cases (intermediate severity), the trabecular plate-nasal septum deviates to the right; no foramina cribrosa are found on the right and very few on the left
|
|
• in severe cases, a dorsoventrally expanded nasal septum fails to develop (i.e. shortened dorsoventrally)
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• newborns exhibit malformed auditory pinnae
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• the external acoustic meatus is shorter and the tubal cartilage develops in nodules
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• tubal cartilage develops in nodules
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hearing/vestibular/ear
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• newborns exhibit malformed auditory pinnae
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• the external acoustic meatus is shorter and the tubal cartilage develops in nodules
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• tubal cartilage develops in nodules
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• the cochlea is reduced and the cochlea fenestra is abnormal in size and orientation
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• at E16.5, the perilyphatic spaces have expanded and spiral laminae are abnormal
• a cartilaginous shelf separates the cochlea from the scala vestibuli
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• the cochlea completes roughly only one coil instead of one and a half
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• at E16.5, the lateral SCC has a complete but shorter cartilaginous canal
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• at E16.5 and P0
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• at E16.5 and P0
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• at E16.5, the pars canicularis is malformed and hypoplastic, as the anterior and posterior SCCs do not form, while the pars cochlearis is smaller
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• the course of stapedial artery is variably affected
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• the malleus is caudally extended and thickened at the level of the manumbrium
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• the malleus has a smaller than normal processus brevis
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• at P0, the epitympanic recess is expanded
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• at P0, the tegmen tympani (TT) is hypertrophic
• the TT maintains a prolonged synovial contact with the malleus and incus, and it shares origins for the tensor tympani with a novel structure ("os paradoxicum") and the gonial
• notably, the stapes, styloid process and incus are all present
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• the tympanic is slightly smaller and thicker
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nervous system
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• at E10.5, axonal defects are noted in the trigeminall ganglion, the processes of the hypoglossal nerve, the autonomic ganglion chain, and the dorsal root ganglion
• at later stages, trigeminal nerve axons extend further into the branchial arches, albeit with abnormal orientations
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• in severe cases, paraseptal cartilages and the vomeronasal organ fail to deveop
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• at E9.0-E13.5, homozygotes display an open neural tube; the defect is generally centered around the midbrain but can extend rostrally and caudally in severe cases
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exencephaly
(
J:56559
)
|
• 28% of newborns display exencephaly
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• at E10.5, the trigeminal ganglion is smaller than normal, its root is malformed, and it has reduced axonal projections into the mesenchyme
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respiratory system
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• in most cases, nasal bones are dysmorphic
|
|
• in most cases
|
|
• in most cases, the tectum nasi, solum and paries nasi prominences and associated turbinates are hypoplastic
|
|
• newborns display reduced nasal capsular breadth, with chondrocranial and dermatocranial defects in and around the nasal capsule and mesethmoid
• in severe cases, newborns show a symmetric near aplasia of the capsule and mesethmoid
• small, cartilaginous spicules are the only remnants of the side walls of the nasal capsule
• in less severe cases, cartilages in the floor of the nasal capsule are hypoplastic and often associated with a rudimentary vomeronasal organ
|
|
• in severe cases, the posterior nasal capsule and mesethmoid are reduced, with no evidence of a developing nasal epithelium, true tectum or solum
• in less severe cases, rudimentary branches of the nasal epithelium are present
|
|
• in severe cases, paraseptal cartilages and the vomeronasal organ fail to deveop
|
|
• in most cases (intermediate severity), the trabecular plate-nasal septum deviates to the right; no foramina cribrosa are found on the right and very few on the left
|
|
• in severe cases, a dorsoventrally expanded nasal septum fails to develop (i.e. shortened dorsoventrally)
|
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• the larynx is displaced caudally, well back from the pterygoids and tympanic cavity
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• the superior cornu of the thyroid cartilage (derived from the fourth branchial arch) fails to form
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skeleton
|
• newborns exhibit variable abnormalities in all cranial bones
• only a few abnormalities are detected in post-cranial axial and appendicular skeleton
|
|
• at E13.5 and E15.5, Meckel's cartilage is shorter and its proximal shaft is severely dysmorphic; the MC orientation deviates twice
|
|
• at E13.5 and E15.5, Meckel's cartilage is shorter than normal
|
|
• all non-exencephalic newborns have calvarial roofs (calottes) with small, hypomineralized parietal and interparietal bones
• in contrast, frontals appear to exhibit normal mineralization
|
|
• all non-exencephalic newborns display small, hypomineralized interparietal bones
|
|
• all non-exencephalic newborns display thicker occipital arch cartilages that expand rostrocaudally
|
|
• all non-exencephalic newborns display small supraoccipital bones with a reduced degree of hypomineralization
|
|
• all non-exencephalic newborns display small, hypomineralized parietal bones
|
|
• alisphenoid bones are slightly dysmorphic
|
|
• the pterygoids have an abnormal amount of chondroid bone and secondary cartilage
|
|
• squamosal bones are slightly dysmorphic
|
|
• extensive chondroid bone develops along the incisive alveolar bone at the tips of the dentary
• the incisivium is broader and shorter than normal
• both sets of incisors are shorter and malformed
|
|
• the molar alveolae are shorter, broader and deeper
• the alveolar openings are constricted distally and broadened proximally
• the buccal molar walls are weaker and ventrally reflected
|
|
• the mandicular and maxillary molars display malformed and poorly mineralized crowns
|
|
• the mandicular and maxillary molars display malformed and poorly mineralized crowns
|
|
• a short and abnormal dentary develops around Meckel's cartilage
|
|
• the condylar and angular processes are shorterned, malformed and juxtaposed
|
|
• the condylar and angular processes are shorterned, malformed and juxtaposed
|
|
• the proximal lamina of the coronoid is absent
|
|
• in most cases, the maxillae are dysmorphic
|
|
• in most cases, the premaxillae are dysmorphic
|
|
• in most cases
|
small maxilla
(
J:56559
)
|
• in most cases
|
micrognathia
(
J:56559
)
|
• newborns exhibit micrognathia
|
|
• in most cases, lacrimal bones are small and dysmorphic
|
|
• in most cases
|
|
• in most cases, nasal bones are dysmorphic
|
|
• in most cases
|
|
• in most cases, the tectum nasi, solum and paries nasi prominences and associated turbinates are hypoplastic
|
|
• in most cases, the vomer bones are small and dysmorphic
|
|
• in 88% of homozygotes, ectopic membrane bones (parapalatines) develop caudal to the palatine shelves and rostral to the dysmorphic pterygoids
|
|
• the malleus is caudally extended and thickened at the level of the manumbrium
|
|
• the malleus has a smaller than normal processus brevis
|
|
• newborns display reduced nasal capsular breadth, with chondrocranial and dermatocranial defects in and around the nasal capsule and mesethmoid
• in severe cases, newborns show a symmetric near aplasia of the capsule and mesethmoid
• small, cartilaginous spicules are the only remnants of the side walls of the nasal capsule
• in less severe cases, cartilages in the floor of the nasal capsule are hypoplastic and often associated with a rudimentary vomeronasal organ
|
|
• tubal cartilage develops in nodules
|
|
• the superior cornu of the thyroid cartilage (derived from the fourth branchial arch) fails to form
|
|
• 27% of newborns display a sinusoidal rib angle
|
|
• all newborns display hypomineralized calottes (calvarial roofs)
|
muscle
|
• the medial pterygoid is hypertrophic; its insertion groove is occluded by a broad origin for an abnormal mylohyoid
|
|
• the right side of the rostral tongue is hypertrophied ventrally
|
|
• the course of the lingual duct and the fascicle pattern of the intrinsic tongue musculature is variably affected
|
cardiovascular system
|
• the course of stapedial artery is variably affected
|
digestive/alimentary system
|
• 88% of newborns exhibit primary and secondary palates with variable degrees of clefting
|
|
• 88% of newborns exhibit primary and secondary palates with variable degrees of clefting
|
|
• the right side of the rostral tongue is hypertrophied ventrally
|
|
• the course of the lingual duct and the fascicle pattern of the intrinsic tongue musculature is variably affected
|
embryo
|
• at E9.0-E13.5, homozygotes display an open neural tube; the defect is generally centered around the midbrain but can extend rostrally and caudally in severe cases
|
cellular
|
• at E10.5, axonal defects are noted in the trigeminall ganglion, the processes of the hypoglossal nerve, the autonomic ganglion chain, and the dorsal root ganglion
• at later stages, trigeminal nerve axons extend further into the branchial arches, albeit with abnormal orientations
|
