These functions are essential in properly developing the central nervous system, somites, skeletal muscles, and neural crest-derived cells that are present throughout various cell types in the body. PAX3 controls the neural crest development through regulation of c-RET, TGF-b2, and WNT1 which are essential controllers of migration and differentiation.PAX3 in combination with other transcription factors such as MITF and TRP1 can control melanocyte development. This gene also plays a major role in muscle development as it regulated myoD and myf-5, essential transcription factors in muscle development.The structure of the gene and protein are well understood in research, PAX3 consists of 10 exons and results in major proteins that has 479 amino acids. It has also been found that a majority of the mutations that occur on the PAX3 gene is located on the 2-6 exons. Heterozygous mutation is the basis of the majority of Type 1 Waardenburg Syndrome mutations. Diagnosis
Type 1 Waardenburg Syndrome is sometimes misdiagnosed as Type 2, therefore when measuring dystopia canthorum if present in a certain patient has been set in strict guidelines. There is a biometric index used as well formula to create a discriminant analysis. These measurements are based on three indices, based on the distances of the inner canthal, interpupillary, and outer canthal. This testing of the dystopia canthorum is referred to as the W index. Other features and dysfunctions are used for diagnoses such as hearing loss or pigmentation of the skin and the notable forelock that appears in the hair.
Waardenburg Syndrome Type 1 is a congenital disorder that caused by a mutation in the PAX3 gene that results in abnormal development in the neural crest during early development. Type 1 results in early graying and white forelock and a notable distance between the eyes, noted as dystopia canthorum. Common symptoms of the disease also includes non-progressive hearing loss in majority of patients with Type 1. Patients can display complete or partial heterochromia and hypoplastic blue irides and congenital leukemia. Presentation
Type 1 of the Waardenburg Syndrome’s notable feature is dystopia canthorum. Along with this feature, some patients eyelids are fused medially, resulting in medial sclerae. Inferior lachrymal is moved laterally, along with punctae opposite of the cornea. Other features include high and broad nasal root and also nasi hypoplasia. A squared jaw is reported in some patients. Others present with spina bifida due to the mutation in the neural crest during early development. Other features include the white forelock and graying that occurs in most patients prior to reaching age thirty. In extremely rare cases, the forelock may even be colored red rather than white. The coloring of the forelock may differ from patient to patient. It can appear at birth, or later in the life of those affected and size may vary. It is usually observed in the midline of the hair, but it can appear in other locations as well.