Craniodiaphyseal Dysplasia

Craniodiaphyseal dysplasia can be defined as a rare medical condition, in which excess quantities of calcium accumulated at the level of the skull. This autosomal recessive disorder may contribute to the significant alteration of one’s facial features, having a negative impact on the life expectancy at the same time. This condition is also known as lionitis, due to the physical appearance resembling the one of a lion.The more calcium is deposited at the level of the skull, the narrower the cranial foramina is going to become. The same change can occur at the level of the cervical canal, both changes ultimately leading to death. In the medical world, there are only a few cases recorded, with the majority of the patients having lost their life in the early years. The exact mechanism for which this condition appears has yet to be determined.

History of Craniodiaphyseal dysplasia

From the start, this condition has been described as a severe form of bone dysplasia, being characterized by two primary changes: hyperostosis (excessive bone growth) and sclerosis (tissue hardening). The involvement was clear, with the skull and the bones of the face being affected. The condition was described as a progressive – the more the foramina would narrow, the more severe the neurological impairment was observed to be (in children).The condition was presented as craniodiaphyseal dysplasia somewhere in 1958, by a team of medical specialists, in describing the characteristic features of a pediatric patient. In 1974, another doctor presented three more cases of lionitis, drawing attention to the fact that this condition might have a genetic cause.

Pictures of Craniodiaphyseal Dysplasia

Symptoms of Craniodiaphyseal dysplasia

The symptoms that the patient presents depends on how narrow the cranial foramina has become. One can experience seizures, suffer from the chronic infection of the lacrimal sac and even paralysis. Intellectual disability occurs commonly as an associated complication. Depending on the quantity of calcium deposited at the level of the skull, the person has a modified physical aspect, with the eyes being located at a farther distance from one another.

Craniofacial abnormalities

• Facial aspect begins to the change in the period of early infancy
• Excessive bone growth → paranasal bossing
• Abnormal difference between the eyes (apparent hypertelorism)
• The circumference of the head increases, as the condition continues to progress
• Recurrent infections at the level of the lacrimal sac (caused by the continuous narrowing of the nasolacrimal ducts)
• Nasal obstruction → breathing difficulties → first change (before the appearance of the craniofacial abnormalities).

Neurological abnormalities

• Excessive bone growth → narrower cranial foramina → cranial nerve compression (in particular of the cranial nerves II, VIII)
• Impaired vision (progressive) → blindness
• Impaired hearing (progressive) → deafness
• Other ocular problems
• Strabismus
• Bulging eyes (exophthalmos)
• Loss of binocular vision
• Hypertelorism
• Seizures
• Mental retardation
• Hearing and vision problems might impair normal development.

Other changes

• Impaired growth (short stature)
• Delayed sexual maturation
• Raised intracranial pressure
• Maxilla and mandible enlargement
• Teeth maleruption.

Diagnosis of Craniodiaphyseal dysplasia

Radiographic manifestations

• Hyperostosis + sclerosis (severe) → skull, bones of the face and mandible
• Nasal obstruction
• Sinuses obliteration
• The bones no longer present the normal contour → opacity → thick and homogenous
• Long bones → cylindrical → diaphysis + endosteum + cortical part → thick
• Bones of the hand might present similar changes
• Thickening + sclerosis → other bones → pelvis, clavicle, rib cage
• Sclerosis → vertebral spine → change at vertebral arch → more visible than the ones occurring at the level of the vertebral body (not in all patients)
• Increased bone density → confirmation of disease progression
• Progression → less pronounced changes at the level of the spine and long bones → more pronounced changes at the level of the skull (sclerosis).

Differential diagnosis

The differential diagnosis can be made with the following conditions:

• Camurati – Engelmann disease (diaphyseal dysplasia)
• Van Buchem’s disease (generalized cortical hyperostosis)
• Other craniotubular dysplasias (craniometaphyseal dysplasia, frontometaphyseal dysplasia).

Because of the fact that the changes which are characteristic for this condition are not present at birth but rather appear and evolve during early pregnancy, it is not possible to diagnose this condition in the womb. Further research is necessary to identify the elements that might suggest such problems before the baby is born (for example, related to bone density).

Management

There is no cure for craniodiaphyseal dysplasia and, unfortunately, the current management measures do not guarantee that the condition will not eventually progress to death. The continuous deposits of calcium lead to the narrowing of the cranial foramina, as well as one of the spinal canal and of the nasal passage. Patients suffer severe complications, such as blindness, deafness and breathing difficulties.These are the measures that can be taken for the management of craniodiaphyseal dysplasia:

• Removal of thyroid gland – performed in order to improve the metabolism of thyrocalcitonin
• Surgical decompression of the cranial foramina – this surgical intervention comes with a high risk for the compression of the brain stem (the edema that appears in the post-operative period can cause such complications); it has also been discovered that the decompression only has a short-term benefit, due to the fact that the calcium continues to be deposited at the level of the skull
• Optic nerve decompression – this surgical intervention is part of the management of vision problems, along with the administration of human calcitonin; it has been discovered that this type of procedure can significantly delay the loss of vision in patients suffering from craniodiaphyseal dysplasia
• Synthetic calcitonin – not all patients respond to the administration of synthetic calcitonin but, in some cases, it was discovered that the head circumference had actually decreased; unfortunately, the therapy with synthetic calcitonin leads to a wide range of side-effects, such as nausea, vomiting and abdominal cramps.

Life Expectancy

As the progression of this condition cannot be kept under control and no treatment has been found, the prognosis is negative. Patients suffer from severe headaches, especially in the morning, which can affect their overall level of functionality. Death is caused by the severe compression of the brainstem, as well as by the increased intracranial pressure. In some cases, cardiac failure has been reported. Studies have shown that most patients died between the ages of seven and sixteen years.