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.
Causes of meningocele include teratoma and other tumors of the sacrococcyx and of the presacral space, and Currarino syndrome.A meningocele may also form through dehiscences in the base of the skull. These may be classified by their localisation as occipital, frontoethmoidal or nasal. Endonasal meningoceles lie at the roof of the nasal cavity and may be mistaken for a nasal polyp. They are treated surgically. Encephalomeningoceles are classified in the same way and also contain brain tissue. Myelomeningocele
Myelomeningocele (MMC), also known as meningomyelocele, is the type of spina bifida that often results in the most severe complications and affects the meninges and nerves. In individuals with myelomeningocele, the unfused portion of the spinal column allows the spinal cord to protrude through an opening. Myelomeningocele occurs in the third week of embryonic development, during neural tube pore closure. MMC is a failure of this to occur completely. The meningeal membranes that cover the spinal cord also protrude through the opening, forming a sac enclosing the spinal elements, such as meninges, cerebrospinal fluid, and parts of the spinal cord and nerve roots. Myelomeningocele is also associated with Arnold–Chiari malformation, necessitating a VP shunt placement.Toxins and conditions associated with MMC formation include: calcium-channel blockers, carbamazepine, cytochalasins, hyperthermia, and valproic acid. Myelocele
Spina bifida with myelocele is the most severe form of myelomeningocele. In this type, the involved area is represented by a flattened, plate-like mass of nervous tissue with no overlying membrane.