Congenital microphthalmia (the blepharophimosis-ptosis-epicanthus in-versus syndrome (BPES)) is also known as Komoto syndrome, Waldenberg syndrome, congenital tetralogy of the lid, microphthalmia syndrome, and microphthalmia malformation. The clinical manifestations are lid narrowing, reverse canthus, ptosis and medial canthal distal tetralogy. It was first reported by FAv von Ammon in 1841 and was described in full detail by J Komoto in 1912. In 1921, TJ Dimitry discovered that it was an autosomal dominant disorder. Since then, a number of researchers have been investigating the etiology, mutation types, pathogenesis, clinical features, timing of surgical treatment and surgical methods of BPES. The progress of research in the past 5 years is reviewed. 1. Genetics of BPES BPES is an autosomal dominant disorder that was discovered in 1995 to be caused by a mutation in the FOXL2 gene at locus 3q23. The FOXL2 gene is a single exon gene of 2.7 kb in size and encodes the FOXL2 protein, which includes a DNA-binding domain (forkhead domain) of 110 amino acids and a polyalanine chain of 14 amino acids. The FOXL2 gene, the first identified marker of mammalian ovarian differentiation, is highly expressed in adult follicular cells and has an important role in ovarian parenchymal cell differentiation and maintenance of female fertility.In 1976, C Moraine et al. first identified BPES in association with female infertility. In contrast, congenital microphthalmia is divided into two types according to its presence or absence of premature ovarian failure: type I refers to microphthalmia combined with female infertility and hypogonadism; type II refers to microphthalmia alone with normal ovarian function. A recent study found that a combined mutation assay can detect gene defects in 80% of typical BPES patients, with the causative gene located at 3q23, candidate genes mainly in FOXL2, and intragenic mutations accounting for 80% of the defects, mainly missense mutations, nonsense mutations, frameshift mutations and whole code changes. More than 100 variants of FOXL2 have been identified in different populations of BPES patients, and most of them are missense mutations occurring in the forkhead structural domain. Haghighi et al. reported one case of missense mutation occurring outside the forkhead structural domain and causing severe BPES. The nonsense mutation tends to occur at the 5′ end of the polyalanine chain, and if the mutation occurs before the forkhead structural domain and causes It is noteworthy that both missense mutations causing deletion of the polyalanine chain and nonsense mutations occurring after polyA can cause type I BPES, suggesting that the C-terminus of polyA and The C-terminus of FOXL2 protein has a major role in the maintenance of ovarian function. Fan et al. reported that in one family of type II BPES, a duplication of the FOXL2 gene was found, resulting in an increase in the length of the polyalanine chain to 25 amino acids; in one case of POF, the length of the polyalanine chain was found to be 4 amino acids. was 4 amino acids. Setty et al. showed that mutations that increase the length of the polyalanine chain to 24 and 26 amino acids are dominantly inherited, whereas mutations of 19 amino acids are recessive, suggesting that mutations in FOXL2 are a definitive factor in BPES. deterministic factor. Recently, L′Hote et al. reported that mutations in FOXL2 (p.C134W) are present in more than 95% of patients with adult-type granulosa cell tumors. kim and Bae found that mutant FOXL2 protein is detected in the activated transcription of target genes, which regulate apoptosis, proliferation, and differentiation of granulosa cells. These findings broaden the scope of research on the FOXL2 gene, but whether its mutations are closely linked to other diseases remains to be investigated. In microphthalmia, the horizontal lid fissure is usually < 20.0 mm in length, but the clinical manifestations are lid narrowing, reversible medial canthus, ptosis and medial canthus distal tetralogy. In some patients, this is associated with low nasal dorsum, lower lid ectropion, supraorbital rim hypoplasia, dense thick black eyebrows, and abnormalities of the lacrimal ducts and tear dots (R Kohn, 1983). The canthus is generally divided into four types (S Duke-Eld-er, 1964; CC Johnson, 1978), of which the lid, lid plate, and brow canthus are all derived from extensions of the upper lid skin, whereas the reverse canthus, or lower lid canthus, is also known as the inverted canthus, which is a diagonal upward extension of the lower lid skin through the medial canthus and is usually bilaterally symmetrical. It is usually bilateral and symmetrical. The majority of patients with ptosis have amblyopia, usually bilateral, as well as strabismus, and a high prevalence of refractive error, with statistically significant differences. A rare complication is the combination of nasolacrimal duct obstruction, developmental delay, mental retardation, and microcephaly. The clinical manifestations of BPES were limited to soft tissue deformities without deep bony deformities, thus, it has some significance for clinical surgical treatment. The two most prominent signs in children with BPES are ptosis and the characteristic reverse medial canthus. The anatomical structure of the medial canthal ligament and the levator muscle has prompted scholars to study and explore whether there are some abnormalities that produce these two signs. Huang et al. first reported the histologic and ultrastructural characteristics of the medial canthal ligament in patients with BPES. It was found that the medial canthal ligament in these patients consisted of collagen fibers, a few elastic fibers, and transverse muscle. The collagen fibers were structurally disorganized and the fibrous connective tissue was glassy. It was also observed that the fibroblasts in the collagen fibers underwent nuclear consolidation, resulting in a decrease in the number of fibroblasts. Therefore, the medial canthus in BPES patients has congenital developmental abnormalities itself, and the change of its main component is the degeneration of collagen fibers, which weakens the tensile strength and makes the medial canthal ligament vulnerable to prolonged strain, which may be an important cause of medial canthal distancing. On the other hand, Decock et al. performed the first comprehensive MRI, anatomical, and histopathological study of the levator aponeurosis in patients with BPES. It was found that all patients with BPES had well-structured transverse muscle fibers in the posterior segment of the levator muscle, which were mixed with collagenous tissue and a small amount of fatty degenerative tissue compared with normal tissue controls, and that these tissues had less tensile strength compared with the transverse muscle fibers, indicating that patients with BPES have weaker levator muscle strength than normal. Because of the difficulty in obtaining tissue specimens, there are few studies on the anatomical aspects of the tissue. BPES is a combined eyelid syndrome with multiple deformities, and other factors may influence the pathogenesis, which requires more in-depth research. In children with BPES, refractive error and strabismus may occur due to ptosis. If the child has good visual acuity, surgery should be performed before school age; in the case of severe ptosis that seriously affects visual acuity, surgery should be performed around 3 years of age, otherwise it may cause amblyopia and have a more significant impact on the child. Therefore, some scholars advocate early surgical correction. However, considering that the child is too young to cooperate with the surgery and that it is difficult to estimate the amount of shortening of the levator muscle and the position of the lid margin under general anesthesia, some scholars recommend surgery after the age of 14 years. Li et al. argue differently, saying that if a child <3 years old undergoes ptosis correction, the frontalis muscle is not fully developed, which can lead to poor surgical outcomes and is more difficult to treat. In the past, most scholars have opted for a staged approach to microphthalmia, with stage I medial canthopexy followed by stage II ptosis surgery six months later. However, staging the medial and lateral canthopexy increases the horizontal tension, which can affect the outcome of ptosis correction. In recent years, Sebastid and Bhattacharjee et al. have advocated completing 2 or 3 surgeries at the same time in stage I. This avoids the emotional and financial burden of multiple surgeries and achieves good surgical results while saving hospitalization time. While staged surgery is appropriate for any child with microphthalmia, not all children with microphthalmia are candidates for stage I. Wu et al. suggest that the treatment should be tailored to the severity of the ptosis. If the upper lid covers more than 2.0 mm of cornea when the eye is opened naturally, staged surgery is recommended; if the upper lid covers exactly 2.0 mm of cornea, stage I surgery is possible, with a good result of a lid opening of approximately 4.0 mm. Sebastia et al. concluded that a "Z" shaped correction of the medial canthus with a steel wire ligature and a broad fascial frontalis suspension is very effective during stage I surgery because the steel wire ligature has a higher tension on the medial canthal ligament than other methods of shortening it, ensuring horizontal tension and achieving a satisfactory postoperative result. satisfactory postoperative results. Taylor et al. cited that shortening and fixation of the medial canthal ligament during stage I surgery had a significant effect on reducing the medial canthal spacing. It is important to note that most surgeons who advocate the use of phase I surgery tend to focus on the completion of phase I of medial canthopexy and ptosis revision, but neglect the importance of the sequence of these two critical steps before and after, which directly affects vertical and horizontal eyelid length adjustments. Huang et al. corrected the ptosis by first correcting the medial canthus, then dissociating the medial canthal ligament to fully release the tension between the eyelids, and finally suturing the medial canthal ligaments on both sides to the deep nasal dorsal fascia and adjusting them to the optimal position with satisfactory results. Therefore, for children with BPES, it is important to choose whether the surgery is staged or completed in stage I, depending on their age, parental requirements, and indications. 5. The surgical approach to staged or stage I surgical repair for microphthalmia includes correction of the medial canthus, reduction of the medial canthus distance, and ptosis revision, with canthoplasty if necessary. 5.1 The canthoplasty procedure for congenital microphthalmia is more complex than the canthoplasty procedure for reverse canthus. The classic procedure is the Musta-de method, which is a combination of the "Z" and "Y-V" canthoplasties. Obviously, the Mus-ta-de method has a complex design, numerous incisions, and requires several tiny flaps to be misaligned and transferred within the narrowed area of the medial canthus, resulting in extensive separation, tissue damage, high operational difficulty, and significant postoperative scarring. The rectangular flap was also used in the early stage, especially for children with wide canthal spacing. In addition, there are also a series of modified techniques based on this procedure, such as single "Z", double "Z", and "Y-V". The traditional canthoplasty described above can basically correct reverse canthus, but the design has a vertical incision and the postoperative scar is obvious. This can be interpreted as a transverse longitudinal suture combined with an auxiliary lower lid incision to avoid the formation of a vertical scar in the medial canthus. Li et al. concluded that if the horizontal lid fissure is still less than 22.0 mm after medial canthopexy correction, an external canthoplasty should be performed to achieve a normal lid fissure length. The Von-Ammon, Blascovics, and Fox methods of canthoplasty are available, while Yu Hao et al. used a new method of external canthoplasty for patients with microphthalmos syndrome with more satisfactory results. This method mainly uses the rotating conjunctival flap of the upper lid and conjunctival extensibility to perform an exophthalmos and transfer the conjunctival flap of the upper lid to the new exophthalmos. The advantages are: ① the new canthus is covered by the conjunctiva, avoiding opposite upper and lower lid trabeculae and greatly reducing the risk of postoperative upper and lower lid adhesions; ② the conjunctival extensibility is good, allowing good closure of the trabeculae after adequate peeling; ③ at the end of the surgery, the conjunctiva will heal quickly without scarring even if some of the upper lid conjunctival trabeculae remain and cannot be completely closed; ④ the triangular flap formed by the surgery has a small angle and is sutured to the new canthus without (5) Many patients with microphthalmia have mild lower lid ectropion, and this method uses upper lid tissue rather than lower lid tissue for transfer repair, reducing further impact on the lower lid. In summary, this method is simple to learn and minimally invasive, with definitive results, and is suitable for the canthopexy of patients with microphthalmia. 5.3. Ptosis revision Severe visual problems due to ptosis in children with BPES can have a greater impact on the child. Therefore, it is very important to perform ptosis correction for this group of children. The most widely used procedures for ptosis correction are: levator shortening, broad fascial frontalis suspension, and frontalis flap transfer suspension. Depending on the severity of the ptosis, the appropriate surgical option is chosen. For a broad fascial frontal suspension, a silicone material of similar nature can be used in place of the own broad fascia to perform a frontal suspension with definite postoperative results. For both methods, Sebastia et al. advocate the use of autologous suspension, as the broad fascia is sufficiently tough to suspend and greatly reduces postoperative complications such as bleeding and infection compared to artificial materials. The silicone suspension graft mentioned and advocated by Friedhofer et al. in their article has the advantage of being easier to adjust at the lid margin and creating a more aesthetic eyelid line compared to the autologous broad fascia. Silicone suspension grafts have been shown to be safe for both children and adults after long-term follow-up. In addition, this technique is easy to perform, takes less time to perform, avoids donor area trauma, and has rounded corners and is buried in the muscle layer, which reduces the chance of infection and foreign body exposure. Although shortening of the levator muscle is the preferred procedure and is anatomically and cosmetically correct, we still advocate the use of frontalis flap suspension for these patients with good results because most have severe ptosis, hypoplastic levator muscle, and poor muscle strength in patients with lid slit syndrome. The results were satisfactory. Patients with BPES present with a quadruple combination of reverse canthus, ptosis, widened medial canthus, and narrow lid fissure. New discoveries and breakthroughs in the genetics of this disease are constantly being made. To date, multiple mutation types and corresponding phenotypes have been identified, but the molecular mechanisms of how FOXL2 gene mutations specifically affect protein expression and lead to BPES are not clear. Genetic screening is even more important in younger women with BPES, as early treatment may reduce the consequences of premature ovarian failure. In addition, the relationship between genotype and phenotype still leaves much room for exploration. The treatment of microphthalmia is a complex and comprehensive treatment. We still advocate early treatment for the timing of surgery, while there are advantages and disadvantages of stage I or staged surgery, which should be selected based on the actual situation of the child and the request of the family for a comprehensive evaluation; there are multiple methods of correction for each step of surgical treatment, therefore, we are always improving the surgical methods in order to achieve more aesthetic as well as definite efficacy to meet the needs of more patients Therefore, we are constantly improving our surgical methods in order to achieve more aesthetic and definitive results and to meet the needs of more patients.