Glossary on osseous malformations of the skull and vertebral column

#Acalvaria: Presence of a intact scalp covering the brain, with or without absence of all bones of the cranial vault.

#Acrocephaly/oxycephaly: A short anteroposterior diameter of the skull with a high forehead and flat occiput. The coronal and sagittal sutures obliterate almost simultaneously and produce a pointed skull with marked vertical development as a result of the osteogenic activity of the lambdoid and parietosquamous sutures. The head looks like those in the movie “Cone head”.

#Basilar impression: Upward displacement of the foramen magnum resulted from deformities of the osseous structures at the base of the skull.

#Brachycephaly: Premature closeure of coronal suture and produces a cranial vault that is short in anterioposterior plane (short, broad skull).

#Clinocephaly: (Clino-, Greek, a slope or bend) Craniosynostosis in which the upper surface of the skull is concave, presenting a saddle-shaped appearance in profile (saddle head).

#Craniolacunae (Lückenschädel): Craniolacunae are translucent, sometimes almost transparent areas of thinning of the bones of the cranial vault. They can be seen in Chiari II malformation and other forms of intrauterine hydrocephalus.

#Craniosynostosis: Craniosynostosis refers to the premature abnormal fusion of one or more cranial sutures. It is frequently associated with other malformation of the skull and the brain.

#Craniostenosis: Narrowing of the skull as a result of fused sutures.

#Dolichocephaly: long in the anteriorposterior plane.

#Holoacrania: The whole cranium is absent (the posterior portion of the posterior fossa and cervical spinal canal will be exposed).

#Hypocalvaria/acalvaria: Hypoplasia of the membrane bones of the skull. The brain is usually relatively normal. The standard being that the bones are absolutely small for age. Harris et al. defined it as the "absence of calvarial bones, dura mater and associated muscles in the presence of a normal skull base and fascial bones." Hypocalvaria/acalvaria is probably resulted from a post-neurulation event.

#Kleeblattshädel (cloverleaf skull): marked prominences at the temples and frontal region. This can be the end result of any of the craniosynostosis syndromes, if complete craniosynostosis of all the suture is present.

#Leptocephaly: (Lepto-, Greek, head) A malformation characterized by an abnormally tall, narrow cranium.

#Meroacrania: (mero-, Greek, a part) A part of the cranium is absent (the occipital bones may have formed).

#Metopism: persistence of the frontal suture in adult.

#Microcephalic synostosis: Due to closure of all sutures simultaneously.

#Oxycephaly: See acrocephaly.

#Plagiocephaly: An unsymmetrical condition of the head due to irregular premature obliteration of coronal suture (e.g., premature fusion of only one arm).

#Scaphocephaly: long head with frontal and occipital prominence, frequently due to premature fusion of the sagittal suture.

#Secondary synostosis: This can be due to abnormally low intracranial pressure as in cases of shunted hydrocephalus and in metabolic diseases interfering with control of bone growth such as hypothyroidism.

#Syndromes:

#Apert Syndrome (Type I acrocephalosyndactyly): The cardinal feature of Apert syndrome is craniosynostosis.

Genetics: Autosomal dominant. Apert syndrome always results from a new dominant mutation. This disorder is allelic to Crouzon disease and due to different mutation of the FGFR2 gene (fibroblast growth factor receptor 2 gene) on chromosome 10q25-26. [Wilkie AO et al., 1995]
Molecular pathology:
Specific mutations at two adjacent residues, Ser252Trp and Pro253Arg, predicted to lie in the linker region between extracellular immunoglobulin IgII and IgIII domain of the FGFR2 ligand-binding domain. One of the possibilities is that Apert syndrome arises as a result of increased affinity of mutant receptors for specific FGF ligands which leads to activation of signalling under conditions where availability of ligand is limiting. [Anderson J et al., 1998]
Patients with Pro253Arg mutation seems to be associated with more severe clinical forms [Lajeunie E et al., 1999].
Clinical features: These patients characteristically have acrocephaly, often with irregular craniosynostosis with the coronal suture usually involved early but all sutures will also be eventually involved. There is also malformation of the face, and malformation of the skeleton with synostosis of joints. Complete symmetrical syndactyly of hands and feet (digits II-IV) is common. Mental retardation is inconstant but may be severe. In adolescence, patients develop severe acne, including of the forearm. Fusion of the 5th and 6th cerevical vertebrae is present in 70% of cases, and deafness and optic nerve atrophy are frequent.
CNS malformations: Different types of malformation of the brain including occipital encephalocele and partial or complete agenesis of the corpus callosum may be seen. There may also be gyral abnormalities, megalencephaly, progressive hydrocephalus had non-progressive ventriculomegaly, absent of olfactory tracts and bulbs, malformation of midline thalamic structures, and others.

#Crouzon syndrome:

Genetics: Autosomal dominant. The gene involved is fibroblast growth factor receptor 2 (FGFR2). Several mutationshave been demonstrated and more than half of the cases in one study are new mutations.
Clinical features: The characteristic features include hypoplasia of the maxilla with shallow orbit and proptosis. Craniosynostosis is a constant feature and begins in the first year of life. The coronal suture is involed early and most frequently. However, the shape of the skull is variable. Features in patients with Crouzon syndrome are quite variable. Conductive hearing loss is also common. Seizures may occur in a small proportion of patients but mental retardatio is rare. Abnormalities of the viscera and extremities may be present but on consistent pattern of involvement has been identified.
CNS malformations: Hydrocephalus is rarely seen but increased intracranial pressure is seen in about one-third of the cases in one study.
Prognosis is good if surgical intervention is taken early.

#Jackson-Weiss' syndrome: Four of the most well-known craniosynostosis syndromes- Apert's, Crouzon's, Pfeiffer's, and Jackson-Weiss' syndromes- have mutations in the fibroblast growth factor receptors (FGFRs). [Ades LC et al., 1994], [Jackson CE et al., 1976]

Genetics: Autosomal dominant.

#Klippel-Feil Syndrome: This is a vertebrate segmentation defect characterized by shortness of neck due to reduction in the number of cervical vertebrae or the fusion of multiple hemivertebrae into one osseous mass, with limitation of neck motion and low hairline. It is part of Wildervanck syndrome. There are three main types. The clinical manifestations of type I and III include short neck, low posterior hairline, and limitation of neck movements. Associated malformations include neuroschisis, conjoined nerve roots, spinal malformation, neuroenteric cysts, Chiari II malformation, syringomyelia, diastematomyelia, impaired pyramidal decussation, dermoid tumors, and intramedullary lipomas.

Type I: Extensive fusion abnormalities of the cervical and upper thoracic spine. This type has shor neck but can also be asymptomatic. The infants may also have dysphagia or mirror movements. Neuroschisis and tethering of the cervical spinal cord have also been reported. Mirror movements: Involuntary, symmetrical, identical movements of one side of the lims that is assoicated with a voluntary movement carried out by the contralateral limb. It may or may not be hereditary. They tend to decrease with age but often persist into adulthood. The mechanism is not clear.
Type II: Limited fusion.
Type III: Discontinuous fusions of cervical and lower thoracic or lumbar spine.

#Klippel-Trenaury-Weber syndrome

#Pfeiffer syndrome (Type V acrocephalosyndactyly):

Genetics: Autosomal dominant. There are mutations of fibroblast growth factor receptor 1 gene (FGFR1) on chromosome 8q11.2-p12 in some families. In other families, there are mutations of exon B of fibroblast growth factor receptor 2 (FGFR2). [Mathijssen IM et al., 1998]
Clinical features: Strasbismus, proptosis, hypertelorism, broad thumbs and great toes, mild variable cutaneous anomalies, syndactyly of fingers and toes. Craniosynostosis is always present and the coronal suture is involved.

#Saethre-Chotzen syndrome (Type III acrocephalosyndactyly):

Genetics: Autosomal dominant. The gene is on chromosome 7p21.
Clinical features: There is facial asymmetry and low-set frontal hairline. Facial malformations include ptosis, deviated nasal septum. Craniosynostosis is always present and involve one or both arms of the coronal suture. There is variable cutneous anomalities, syndactyly of fingers and toes.

#Visceral abnormalities: About 10% of patients are associated with congenital heart disease and genitourinary abnormalities.

#Trigonocephaly: triangular shpae to the skull often associated with an upslant of the palpebral fissures and a prominent metopic ridge. This can be caused by premature fusion of the metopic suture.

#Turricephaly: The coronal suture closes first and followed by other premature obliteration of the sagittal suture. There will be brachycephaly with secondary upward expansion of the skull when the sagittal suture close later and results in a tower-shaped head.

#Wormian bone (sutural bone): small irregular bones found along the sutures of the cranium, particularly related to the parietal bone.

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