The following testing regime has been recommended by the European Skeletal Dysplasia Network:
Level 1: COMP (exons 10–15) and MATN3 (exon 2)
Level 2: COMP (exons 8 & 9 and 16–19)
Level 3: COL9A1 (exon 8), COL9A2 and COL9A3 (exon 3)All those genes are involved in the production of the extracellular matrix (ECM). The role of COMP gene remains unclear. It is a noncollagenous protein of the ECM. Mutations in this gene can cause the pseudoachondroplasia (PSACH). It should play a role in the structural integrity of cartilage by its interaction with other extracellular matrix proteins and can be part of the interaction of the chondrocytes with the matrix and it is also a potent suppressor of apoptosis in chondrocytes. Another role is maintaining a vascular smooth muscle cells contractile under physiological or pathological stimuli.Since 2003, the European Skeletal Dysplasia Network has used an online system to diagnose cases referred to the network before mutation analysis to study the mutations causing PSACH or MED.COL9A1, COL9A2, COL9A3 are genes coding for collagen type IX, that is a component of hyaline cartilage. MATN3 protein may play a role in the formation of the extracellular filamentous networks and in the development and homeostasis of cartilage and bone.In the recessive form, the DTDST gene, also known as SLC26A2, is mutated in almost 90% of the patients, causing diastrophic dysplasia. It is a sulfate transporter, transmembrane glycoprotein implicated in several chondrodysplasias. It is important for sulfation of proteoglycans and matrix organization.
They present often as tonic eyelid opening with some changes in breathing coupled with pupillary dilation, urinary incontinence, increased heart rate, and flushing can occur.Nonconvulsive status epilepticus occurs in about 50% of patients. The seizures can cause sudden falling often leading to injury. These "drop attacks" are typically the first manifestation of LGS. The attacks are characterized by a single, generalized monoclonic jerk that precedes tonic contraction of axial muscles. EEG findings
Findings that strongly suggest LGS include consistent slow spike-wave (< 3 hertz [Hz]) on awake EEG. The complexes typically consist of a spike (duration < 70 milliseconds) or a sharp wave (70-200 milliseconds), followed first by a positive deep trough, then a negative wave (350-400 milliseconds). Not every wave is preceded by a spike. Bursts increase and decrease without clear onset and offset. Slow spike waves may occur during seizure or between seizures, or may occur in absence of any observable clinical changes which helps distinguish pattern from extended 3-Hz spike-wave discharges. Ocular abnormality
Ocular abnormalities affect around 90% of children. They can present as refractive error, strabismus, cortical visual impairment, and premature retinopathy. Causes
The disease pathophysiology is mostly unknown, but some evidence implicates cortical hyperexcitability occurring at critical periods of brain development.There are two types of LGS: idiopathic and secondary. The cause of the idiopathic subtype is unknown. Secondary LGS occurs when an identifiable underlying pathology is responsible. The most common type of LGS (70–78%) is secondary. These patients tend to have a worse prognosis than those with idiopathic LGS.