Pyknodysostosis

Dwarfism with osteosclerosis. Congenital sclerosing osteodysplasia.

Toulouse-Lautrec Disease.

The disease is named after the French painter Henri de Toulouse-Lautrec, since Maroteaux and Lamy, the first describers of pyknodysostosis, concluded from complaints found in letters to his friends and relatives that he was suffering from pyknodysostosis, although this has been the subject of vivid debate.

NB: Some authors consider pyknodysostosis synonymous with Maroteaux-Lamy Syndrome. Although it is true that these two French physicians were the first to describe and name pyknodysostosis, the name Maroteaux-Lamy Syndrome (which is used for at least four different syndromes) most often refers to mucopolysaccharidosis type VI.

Nearly 150 cases have been reported.

Autosomal recessive with parental consanguinity being a known risk factor. The mutation has been mapped to 1q21.

Pyknodysostosis results from a gene defect affecting cathepsin K, the only lysosomal cysteine protease with high expression in osteoclasts. This fact, in combination with the highest type I collagenolytic, elastinolytic, and gelatinolytic activities of all cysteine proteases, suggests that cathepsin K plays a key function in bone matrix resorption. Pyknodysostosis can therefore be considered a skeletal dysplasia secondary to cathepsin K deficiency, which makes it a lysosomal disease. The principal site of action for cathepsin K is the subosteoclastic space into which the enzyme is secreted for bone matrix degradation. The process of bone resorption is characterized by solubilization of inorganic mineral and subsequent proteolytic degradation of the organic matrix, primarily type I collagen. The osteoclast number in pyknodysostosis is normal, but the area of demineralization surrounding each individual osteoclast is enlarged. Ultrastructural examination of these osteoclasts shows big, abnormal intracytoplasmic vacuoles filled with collagen fibrils from bone. It seems therefore that step one (demineralization) of normal bone resorption is intact, whereas step two (degradation of the organic matrix) is defective. The inadequate resorption and remodeling of bones in pyknodysostosis leads to abnormally dense and brittle bones.

Clinical features and radiologic appearance of bones (osteosclerosis, increased thickness of the trabecular bone as a result of increased density).

Short stature (adult height usually less than 150 cm [59 inches] for males) caused by short limbs, large, disproportionate head with frontal and occipital bossing, delayed suture closure and prolonged persistence of fontanels, and lack of frontal sinuses. The midface is hypoplastic with a prominent nose, grooved palate, and hypoplasia of the mandibular angles, making these patients prone to obstructive sleep apnea. The clavicles are affected by partial or complete aplasia. Progressive acro-osteolytic dysplasia affects the distal phalanges of fingers and toes with dystrophic, flattened, grooved, and brittle nails. Spondylolysis may occur at the L4-L5 level and scoliosis is a common finding. Dentition anomalies include delayed eruption and irregularities of the permanent teeth, with or without partial anodontia. The brittle bone results in fractures secondary to minimal trauma and the sometimes blue appearance of the sclera may initially result in the diagnosis of osteogenesis imperfecta. The intelligence is usually normal for the chronologic age but mild mental retardation has been reported in some cases. Rarely, hyperostosis can lead to the development of hematological complications (pancytopenia) similar to those found in osteopetrosis. A low concentration of insulin-like growth factor-1 has been reported for many patients suffering from pycnodysostosis. Therapy with exogenous growth hormone showed improvement in the linear growth. A significant abnormality of the hypothalamic-pituitary, thyroid, or adrenal axis in these patients is generally not found.

Check mouth opening and other signs predictive for difficult airway management. Assessment of obstructive sleep apnea should include a polysomnographic study or, at least, continuous sleep pulse oximetry. If obstructive sleep apnea is present, its consequences on the cardiovascular system (cor pulmonale) should be evaluated and nasal continuous positive airway pressure therapy started prior to elective surgery. The teeth are generally in poor condition and need to be assessed. Laboratory investigations should include at least a CBC (anemia or even pancytopenia) and an arterial blood gas analysis (together with a chest radiograph) in the presence of scoliosis.

Careful positioning is mandatory because of increased bone fragility. Although not reported, direct laryngoscopy and tracheal intubation could be difficult secondary to midface hypoplasia and anomalies of the mandible and the clavicles. In the presence of obstructive sleep apnea, nasal continuous positive airway pressure should be resumed in the recovery room and close postoperative monitoring for apnea is recommended. Neuraxial blockade may turn out to be difficult because of scoliosis and a radiograph of the lumbar spine might be helpful. Infraclavicular approach for brachial plexus anesthesia and puncture of the subclavian vein may be difficult because of partial aplasia of the clavicles.

Avoidance or at least careful titration of opioids and benzodiazepines is recommended if obstructive sleep apnea is suspected.

Cleidocranial Dysplasia: Generalized skeletal dysplasia resulting in defects in the development of skull, clavicles, pelvis and dental abnormalities.

Osteopetrosis: A heterogenous genetic disorder resulting in increased bone mass caused by defective bone resorption. Depending on the mode of inheritance, its course can be either uniformly fatal with pancytopenia, recurrent pathological fractures, blindness, and other neurological symptoms, or exist in a much milder form with later manifestation and favorable prognosis.

Dysosteosclerosis: Genetic disorder with unfavorable prognosis manifesting with blindness, mental retardation, and characteristic skeletal changes.

Osteogenesis Imperfecta: An autosomal dominant disorder with multiple bone fractures (postand antenatal). Four major types are known. Type I is the one most frequently encountered in anesthesia.