Research in animal models has led to the idea that the dura mater plays an important role in determining closure or patency of the suture. In contrast to the dura mater it appears that the periosteum is not essential in causing closure or patency. Instead of describing the abnormalities in structure and form, research focuses nowadays at decoding the molecular interactions that underlie them. Based on data from quantitative real-time PCR on samples of suture junctions during development, cranial suture fusion in mammals is a tightly orchestrated expression of genes in specific temporal order, leading to endochondral ossification. Despite the progress that has been made, many things are still not understood about the suture biology and the exact causative pathways remain yet to be completely understood.Multiple potential causes of premature suture closure have been identified, such as the several genetic mutations that are associated with syndromic craniosynostosis. The cause of nonsyndromic craniosynostosis however, is still greatly unknown. Most likely, a role is played by biomechanical factors, as well as environmental, hormonal and genetical factors.New insights have given fuel to a debate whether there might be an intrinsic factor causing the premature fusion of the sutures. Brain structures of children with craniosynostosis were evaluated using magnetic resonance imaging. Differences were seen compared with the brain structures of normal children. The question now is whether these differences are caused by the craniosynostosis, or are the cause of craniosynostosis. Biomechanical factors
Biomechanical factors include fetal head constraint during pregnancy. It has been found by Jacob et al.
Noonan syndrome with multiple lentigines (NSML) which is part of a group called Ras/MAPK pathway syndromes, is a rare autosomal dominant, multisystem disease caused by a mutation in the protein tyrosine phosphatase, non-receptor type 11 gene (PTPN11). The disease is a complex of features, mostly involving the skin, skeletal and cardiovascular systems, which may or may not be present in all patients. The nature of how the mutation causes each of the conditions symptoms is not well known; however, research is ongoing. It is a RASopathy. Noonan syndrome with multiple lentigines is caused by a different missense mutation of the same gene. Noonan syndrome is fairly common (1:1,000 to 1:2,500 live births), and neurofibromatosis 1 (which was once thought to be related to NSML) is also common (1:3500); however, no epidemiological data exists for NSML. Signs and symptoms
An alternative name of the condition, LEOPARD syndrome, is a mnemonic, originally coined in 1969, as the condition is characterized by some of the following seven conditions, the first letters of which spell LEOPARD, along with the characteristic "freckling" of the skin, caused by the lentigines that is reminiscent of the large cat. Lentigines — Reddish-brown to dark brown macules (surface skin lesion) generally occurring in a high number (10,000+) over a large portion of the skin, at times higher than 80% coverage. These can even appear inside the mouth (buccal), or on the surface of the eye (scleral).