UNASSIGNED: Geleophysic dysplasia (GD) and Weill-Marchesani syndrome (WMS) are two rare genetic disorders that are classified as acromelic dysplasias and have many common features that overlap clinically and genetically in some patients. Both diseases are characterized by acromelic features, including short stature, brachydactyly, joint limitations, and cardiac involvement. WMS is distinguished from GD mainly by ocular abnormalities, including high myopia, microspherophakia, ectopia lentis, and glaucoma and the absence of the life-threatening airway stenosis and early lethality. These two syndromes are allelic diseases of the FBN1 gene, with the gene families including A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS) and latent transforming growth factor-beta-binding protein (LTBP). Although the ADAMTSL2 gene has been associated only with GD within the acromelic dysplasias, there have been reports of patients with ADAMTSL2-related GD exhibiting ocular abnormalities that resemble WMS.
UNASSIGNED: We present a 24-year-old female patient with microspherophakia, ectopia lentis, myopia, short stature, joint stiffness, thick skin, short hands and feet, and cardiac valve disease consistent with WMS. The virtual panel analysis, including WMS and GD-related genes, revealed a homozygous c.493 G>A (p.Ala165Thr) variant in the ADAMTSL2 gene (NM_014694.4), which has been previously reported in a geleophysic dysplasia patient.
UNASSIGNED: Mounting evidence suggests that GD and WMS may be allelic diseases of the ADAMTSL2 gene.

UNASSIGNED: To report a rare case of microspherophakia and lens subluxation in a young patient with Klinefelter syndrome who underwent cataract surgery, emphasizing the importance of a thorough general health assessment and anamnesis prior to cataract surgery.
UNASSIGNED: The case concerns a 52-year-old male referred for phacoemulsification under general anesthesia. A review of literature was performed.
UNASSIGNED: Preoperative assessment revealed a corticonuclear cataract in both eyes, with dislocation of the crystalline lens in the left eye in an area of zonular dehiscence. Upon careful examination, both eyes showed a microspherophakic lens with an increased lens thickness and the lens equator being visible over 360° in the left eye. The patient denied any trauma or medical conditions. His medical health record revealed the coexistence of Klinefelter syndrome (47, XXY). The association between Klinefelter syndrome and microspherophakia has only once been reported in the literature. Intraoperatively, a more cautious approach was withheld and a capsular tension ring was used. Postoperative outcome was successful with good visual outcome and no interoperative complications.
UNASSIGNED: This case report highlights the importance of proper preoperative assessment before cataract surgery, especially in unusual cases such as early-onset cataract and/or lens subluxation. In addition, it stresses the importance of a systemic and/or genetic evaluation in patients with microspherophakia and an ophthalmological examination in patients with Klinefelter syndrome.

The crystalline lens is an important structure in the eye that starts to develop as early as the 22nd day of gestation, with further differentiation that continues after the induction. Congenital anomalies of the lens may involve the size, shape, and position of the lens. They may sometimes be associated with anterior segment dysgenesis or persistence of the tunica vasculosa lentis and hyperplastic vitreous and hyaloid system. Manifestations of anomalies of the lens shape are usually seen in early or late childhood however may sometimes be delayed into adulthood based on the level of visual impairment or the presence or absence of any syndromic associations. While lens coloboma has more often been reported in isolation, the more commonly implicated genes include the PAX6 gene, lenticonus in particular anterior is often part of Alport syndrome with extra-ocular manifestations in the kidneys and hearing abnormalities due to mutations in the alpha 5 chain of the Type IV collagen gene. Recognition of these manifestations and obtaining a genetic diagnosis is an important step in the management. The level of visual impairment and amblyopia dictates the outcomes in patients managed either conservatively with optical correction as well as surgically where deemed necessary. This review discusses the various anomalies of the lens shape with its related genetics and the management involved in these conditions.

Microspherophakia constitutes a rare, mostly bilateral anomaly of the crystalline lens, which is characterized by the presence of an increased lens thickness and reduced equatorial diameter. It is frequently associated with lens subluxation, translating into a high degree of variable lenticular myopia and defective accommodation. The purpose of this report is to describe the treatment of a three-year-old female patient with microspherophakia, with the scleral fixation of an intraocular lens using the z-suture technique. A three-year-old female patient with Marfan Syndrome presented with high bilateral myopia and esotropia. Lens subluxation was perceived, and she was proposed for bilateral surgery. Scleral fixation of the intraocular lens was performed using the z-suture technique. During the five-year follow-up period, she maintained a best-corrected visual acuity of 20/20 in both eyes wearing bifocal glasses.  Microspherophakia is a rare but impactful condition, frequently related to severe and variable refractive error due to the lens shape and zonule instability. Intraocular lens implantation in the capsular bag is usually impossible, and scleral fixation is a valid alternative. The z-suture technique avoids suture knots and the need for intrascleral flaps, reducing the risk of suture-related complications.

Microspherophakia is a rare developmental lens anomaly with increased anteroposterior and reduced equatorial diameter. It presents with refractive myopia, shallow anterior chamber, and angle closure glaucoma. It is associated with subluxated or dislocated lens, progressive myopia, defective accommodation, and glaucoma. Glaucoma is the most common vision-threatening complication and mostly requires surgical management that includes trabeculectomy, lensectomy, and drainage implant. A staged or combined procedure can be performed. The purpose of this video is to highlight the advantages of combining parsplana vitrectomy (PPV) with parsplana lensectomy (PPL), scleral fixated intraocular lens (SFIOL), and Aurolab aqueous drainage implant (AADI) in a young patient with advanced glaucoma and gross subluxation. Drainage implants are preferred over filtering surgeries in eyes undergoing vitreoretinal procedures due to the risk of bleb fibrosis and hypotony seen in the latter. The combined procedures should be tailored according to the lens status and severity of glaucoma in each patient.
The purpose of this video is to illustrate a combined quadruple procedure (PPL, PPV, SFIOL, and AADI) in microspherophakic patients with unstable glaucoma and video-based skill transfer to a novice surgeon.
This video illustrates quadruple surgery in a microspherophakic patient with secondary angle closure glaucoma. The authors also emphasize the advantages of a combined quadruple procedure over staged procedure or combined PPL with filtering procedure.
Quadruple procedure can be performed in young microspherophakic patients with advanced glaucoma or at risk of progression and losing central vision along with gross subluxation of lens. It eliminates the need for multiple procedures, the risk of hypotony, and bleb-related complications.
https://youtu.be/KdFjb7acXCI.

UNASSIGNED: Bilateral secondary angle closure glaucoma is a presenting symptom of microspherophakia and ectopia lentis. Characterizing the associated syndrome and confirmation by genetic testing can identify associated systemic abnormalities and provide appropriate genetic counseling.
UNASSIGNED: A 42-year-old woman with severe intellectual disability presented with light perception visual acuity and glaucoma, with intraocular pressure (IOP) in her right and left eyes of 69 and 70 mmHg, respectively. She underwent two sessions of 270-degree laser diode transscleral cytophotocoagulation treatment at a 6-month interval and was prescribed topical anti-glaucoma medication. Her family noticed a progressive decrease in her vision while on treatment for 2 years. She was diagnosed with apparent Weill-Marchesani syndrome, accompanied by angle closure glaucoma and microspherophakia. Cataract surgery and intraocular lens implantation were successful in both eyes and post-operative IOP was controlled with anti-glaucoma medication but her vision did not improve from severe glaucomatous optic neuropathy. Her underlying syndrome was investigated genetically by whole exome sequencing.
UNASSIGNED: Sequencing showed a pathogenic variant in ARID1B, c.3955dupC (p.Gln1319Profs*14), diagnostic of Coffin-Siris syndrome. This is the first report of Coffin-Siris syndrome associated with microspherophakia and angle closure glaucoma.
UNASSIGNED: Bilateral angle closure glaucoma from ectopia lentis in patients with genetic syndromes could be an indicator of microspherophakia in adulthood. Ophthalmological surveillance is important in patients with Coffin-Siris syndrome.

We present the long-term results of the implantation of a capsular tension ring (CTR) and Ahmed capsular tension segments (CTS) together for the management of mikrospherophakia in a 35-year-old female patient. The patient had uncontrolled secondary angle-closure glaucoma, despite previous laser peripheral iridotomy, and visual impairment due to lenticular myopia. Clear lens extraction was performed under general anesthesia. The capsular bag was stabilized with a classical CTR and two Ahmed CTSs sutured to the sclera. A single-piece hydrophobic acrylic intraocular lens (32.0 D for the right and 30.0 D for the left eye) was implanted in the capsular bag. The anterior chamber depth was stable, and intraocular pressure (IOP) was 10-12 mmHg in both eyes in the early post-operative period. The bag complex gradually moved forward, IOP gradually increased, and the left eye underwent trabeculectomy surgery in the 4th year of follow-up.

Weill-Marchesani syndrome (WMS) manifests as ectopia lentis (EL), microspherophakia and short stature, which is caused by ADAMTS10, LTBP2, or ADAMTS17 gene defects. This study aims to investigate the characteristics and genotype-phenotype correlations of WMS with ADAMTS17 mutations. WMS patients with ADAMTS17 variants were identified by whole-exome sequencing from 185 patients with EL. All the included patients underwent comprehensive ocular and systemic examinations. ADAMTS17 variants were reviewed from included patients, published literature, and public databases. Bioinformatics analysis, co-segregation analysis, species sequence analysis, and protein silico modeling were used to verify the pathogenic mutations. A total of six novel ADAMTS17 mutations (c.1297C > T, c.2948C > T, c.1322+2T > C, c.1716C > G, c.1630G > A, and c.1669C > T) were identified in four WMS probands in our EL cohort (4/185, 2.16%). All probands and their biological parents presented with apparent short stature compared with the standard value. In particular, one child was detected with valvular heart disease, which has not previously been reported in patients with ADAMTS17 mutations. Conserved residues were greatly affected by the substitution of amino acids caused by these six mutations. Short stature could be considered a clue for EL patients with ADAMTS17 mutations, and much more attention needs to be paid to heart disorders among these patients. This study not only reported the characteristics of ADAMTS17 mutation-related WMS but also helped to recognize the genotype-phenotype correlations in these patients.

Microspherophakia is a rare congenital anomaly characterized by an abnormally small and spherical crystalline lens, which can be associated with several systemic syndromes. We present an extremely rare case of bilateral anteriorly displaced microspherophakia in a female child with Marfanoid habitus. The patient displayed phenotypic features resembling Marfan syndrome, including tall stature, muscle hypotonia, dolichostenomelia, and increased arm span than body length. However, unlike Marfan syndrome, Marfanoid habitus is not associated with mutations in the fibrillin-1 gene. The association between microspherophakia and Marfanoid habitus is a unique presentation that has not been reported in the literature. This case report aims to increase awareness of microspherophakia as a possible ocular association of Marfanoid habitus.

UNASSIGNED: Weill-Marchesani syndrome 4 (WMS4) is caused by ADAMTS17 gene variant and clinical abnormalities including lenticular myopia, ectopia lentis, glaucoma, microspherophakia, brachydactyly, and short stature. Due to free of heart defects and joint stiffness compared with other WMS forms, WMS4 has an insidious onset and is often misdiagnosed as high myopia. We combined multiple imaging biometry and whole-exome sequencing to diagnose a case of WMS4 with a 3-year follow-up.
UNASSIGNED: An 8-year-old boy presented to our ophthalmology department with progressive myopia for 1 year. He had high myopia in both eyes with normal funds, intraocular pressure, and axial length. Ocular examination revealed thicker lenses (right 4.38 mm, left 4.31 mm) with a smaller equatorial diameter (right 7.33 mm and left 7.17 mm) compared to normal children of the same age. Finger length measurement indicates brachydactyly. Whole-exome sequencing identified compound heterozygous missense variants c.2984G > A (p.Arg995Gln) and c.2254A > G (p.Ile752Val) in the ADAMTS17 gene. During the 3 years of follow-up, the thickness of lenses increased significantly (right 4.49 mm, left 4.48 mm), but the equatorial diameter of the lenses had no significant change (right 7.32 mm, left 7.21 mm). As the equivalent lens power increased, the patient\'s myopia spherical refractive error rose accordingly. Although the anterior chamber angle remained open during follow-up, the intraocular pressure increased to right 20.4 mmHg and left 19.6 mmHg, Iridodonesis and short stature were present.
UNASSIGNED: This case report highlights the abnormal thickening of the lens in WMS4 compared to the physiological thinning process during childhood. Comprehensive clinical examinations and genetic testing may improve diagnosis, which allows early therapeutic interventions for complications and better visual outcomes for the patient.