Dyggve-Melchior-Clausen Syndrome

Short-spine-type dwarfism associated with mental retardation and skeletal abnormalities.

Only 58 cases have been reported in the literature. Seems to occur more frequently in Lebanon.

Autosomal recessive. Linkage studies localized the responsible genes to chromosome 18q12-21.1. This gene seems to be involved in normal skeletal development and brain function.

Electron microscopy of chondrocytes shows dilated cisternae of rough endoplasmic reticulum, containing fine granular or amorphous material. Protein accumulation within the rough endoplasmic reticulum has been hypothesized to be secondary to an enzyme defect that has not been characterized.

Clinically, thoracic deformities in the form of barrel chest become visible in the first 18 months of life. Radiographs of the iliac crests show a characteristic, lace-like appearance, which is caused by an irregular pattern in the bone tissue deposits at the osteochondral junction. Abnormal enchondral ossification and absent columnarization of chondrocytes are found in the growth plates. The vertebral bodies are characteristic, presenting with double-hump endplates associated with a central constriction (platyspondyly). These signs usually are present by age 4 years and become more prominent with increasing age.

Phenotypically, patients share some features of Morquio and Hurler syndromes. In fact, the disorder initially was named Morquio-Ullrich disease. Affected patients present with dwarfism because of both short trunk and short limbs. The mean adult height is approximately 130 cm (51.2 in). They also have a coarse facies, although the degree is highly variable, ranging from almost normal to very severe, where the bulky jaws and microcephaly are striking. The neck is short. Patients have a variable degree of odontoid hypoplasia, which may lead to atlantoaxial instability and place them at risk for complications related to spinal cord compression. The chest is barrel shaped, and malalignment of the spine with kyphoscoliosis is common. The hands and feet are broad, and the fingers might be clawed. Dislocation of hips and shoulders are common (secondary to dysplastic joints). Although mental retardation is present, general health is otherwise good and survival into adulthood is the rule.

Short stature in association with the spine deformity leads to restrictive lung disease so pulmonary function tests are recommended, although cooperation may be limited. Blood gas analysis and echocardiography (cor pulmonale) may be warranted, depending on the results of the lung function tests. Obtain flexion and extension radiographs or CT scans of the cervical spine to rule out atlantoaxial instability. Anxiolytic or sedative premedication may be helpful in the presence of mental retardation.

Difficult tracheal intubation is likely (even without atlantoaxial instability) because of the presence of a short neck, prominent, big jaws, macroglossia, and limited mouth opening. Tracheal intubation should be performed either fiberoptically or, if possible, conventionally with inline stabilization of the cervical spine. Restrictive lung disease may render ventilation and oxygenation more challenging and may preclude the use of neuraxial regional anesthesia. Proper patient positioning is difficult because of atlantoaxial instability, dislocations (hip, shoulder), deformities, and contractures affecting the musculoskeletal system.

Titrate sedation carefully to avoid respiratory depression in the presence of restrictive lung disease.

Smith-McCort Dysplasia/Dwarfism: Allelic disorder similar to the Dyggve Melchior Clausen syndrome, with the only significant difference being the absence of mental retardation.