Patients experience optic atrophy due to progressive cranial nerve compression, which may lead to nystagmus or even blindness in severe cases.Other neurological abnormalities include intellectual disability, speech and psychological deterioration. Convulsions and status epilepticus are also present in patients, however the mechanisms for the development of these features are unknown. Patients also experience cranial nerve damage resulting from progressive cranial pressure. Pathogenesis
DSS is classified as an autosomal recessive disease(OMIM 224300), but it is also identified as an X-linked recessive inheritance in certain families. The total number of genes that are responsible for causing the disease and the correlation between genotype and phenotype remains unclear. Multiple gene mutations were identified in different patients via whole genome sequencing, therefore it is presumed that DSS is genetically heterogeneous. TCIRG1 mutation
The TCIRG1 gene is present in chromosome locus 11q13, which encodes for the a3 subunit of vacuolar H+ ATPase (V-ATPase) that is unique to osteoclasts. The a3 subunit is responsible in anchoring the vacuolar proton pump to the ruffled membrane of osteoclasts. The V-ATPase is important in mediating the transport of hydrogen ions into the resorption lacunae, which is a pit on the bone surface enclosed by the osteoclast for bone resorption. The accumulation of ions in the lacuna facilitates the decomposition of hydroxyapatite crystals by creating an acidic environment, resulting in bone resorption. Mutation of the gene results in osteoclast-rich osteopetrosis due to poor translation and altered structure of proton pump structure, which is normally involved in large amounts of osteoclast activity leading to absorption of bone tissue.
Platyspondyly development begins with generalised osteosclerosis, then subsequent interspersing sclerotic bands develop within vertebral bodies with normal bone density, showing radiolucency. Diagnosis
Medical diagnosis of DSS involves various examinations and evaluations. This usually includes physical examinations, medical history evaluations, assessment of signs and symptoms, laboratory tests and image studies. Biopsy may also be required if necessary.Signs and symptoms of DSS show similarities with multifarious disorders and diseases such as osteosclerosis, H syndrome and Pyle disease. As such, it is likely that DSS is consequently incorrectly identified as osteopertrosis. Therefore, additional tests may be performed in order to arrive at a definitive diagnosis. Prognosis and management
Overall the disease has a poor prognosis, with treatment mainly focusing on palliation and comfort care.As the mechanism and clinical course of DSS remains unclear, definitive treatment is not available for patients. Bone marrow transplant may improve skeletal abnormalities, however it is improbable the transplant will ameliorate the unexplained neurological deteriorations. In addition, the surgery may not be suitable for every patients as the underlying genetic cause of the disease varies amongst patients. Advice of control and reduction in excessive calcium intake may be recommended by physicians to ensure circulating levels of parathyroid hormones are normal to induce and maintain bone resorption. == References ==