|Year : 2020 | Volume
| Issue : 1 | Page : 10
Weil–Marchesani syndrome: A case report and literature review
Carlos Emiliano Rodríguez Lopez, Guadalupe Fernando Mora González, Gerardo Daniel Jáuregui García
Puerta de Hierro Medical Center, Zapopan, Jalisco, México
|Date of Submission||11-Feb-2020|
|Date of Acceptance||10-Mar-2020|
|Date of Web Publication||23-Apr-2020|
Dr. Carlos Emiliano Rodríguez Lopez
Avenida Universidad 185 Int. V10, Zapopan, Jalisco CP 45066
Source of Support: None, Conflict of Interest: None
Weill–Marchesani syndrome is a rare connective tissue disorder, with a poorly understood etiology that has been primarily related to hereditary genetic factors, including mutations in ADAMTS10 and fibrillin-1. Clinically, it is characterized by a phenotype of short stature and brachydactyly, associated with joint stiffness and eye problems that begin to be noticed in childhood. There is little information about this disease in the Mexican population. This is a description of the case of a 17-year-old female patient with clinical feature compatible with this syndrome, as well as a brief review of the literature on this entity. The knowledge of this syndrome is important to achieve a timely diagnosis and prevent the complications associated with it.
Keywords: ADAMTS10, braquidactilia, ectopia lentis, fibrilina 1, glaucoma, microesfrofaquia
|How to cite this article:|
Lopez CE, González GF, García GD. Weil–Marchesani syndrome: A case report and literature review. Pan Am J Ophthalmol 2020;2:10
| Introduction|| |
Weill–Marchesani syndrome (WMS), also known as microspherophakia-brachydactyly syndrome, is a rare and generally inheritable connective tissue disorder. The etiology of this syndrome is associated with genetic mutations. The autosomal recessive inheritance represents 45% of the cases in the literature and the autosomal dominant 39%, the rest of the cases are considered sporadic.
Mutations in ADAMTS10 and fibrillin-1 (FBN1) have been linked as major causes of WMS. The ADAMTS10 protein is essential for extracellular matrix function and is involved in the development of the eyes, heart, and skeleton in humans. It has been suggested that exchanging a leucine for hydrophilic polar glutamine within the hydrophobic core disrupts the normal function of ADAMTS10. Inactivation of ADAMTS10 in mice causes the same symptoms as in humans. The FNB1 protein has been identified as a structural macromolecule that polymerizes microfibrils and helps to provide resistance and flexibility to connective tissue.
The ADAMTS 17 protein is a member of the metalloproteinase family. It is believed that its bind to the extracellular matrix and has recently been associated with the pathophysiology of WMS., The beta-binding protein of latent transforming growth factor 2 (LTBP2) is an extracellular matrix protein that is associated with microfibrils that contain FBN1; this protein has also been considered in the etiology of WMS. Through the use of modern sequencers, a mutation with a homozygous reading frameshift in the LTBP2 gene has been detected in two affected patients of the same family.
The various genetic abnormalities mentioned cause a connective tissue disorder characterized by a phenotype of short stature and brachydactyly, associated with joint stiffness and eye problems, typically recognized in childhood. Common ocular manifestations include spherophakia, elevated myopia, and ectopia lentis toward the lower nasal quadrant. In severe cases, the lens can be dislocated into the anterior chamber.
It is suspected that spherophakia is caused by an abnormality in the zonular fibers that causes the lens to increase its anteroposterior diameter, taking a spherical appearance instead of tending to a normal biconvex shape. Dysgenesis of the anterior segment is associated with the failure of migration and differentiation of neural crest cells. The increase in lens thickness results in a small anterior chamber and narrow angles. The lens tends to move forward due to zonular relaxation; this leads to pupillary blockage and an increase in intraocular pressure (IOP).
| Case Report|| |
17-year-old female patient, Mexican and originally from the town of Reyes, municipality of Armería in the state of Colima. Direct interrogation was conducted in the presence of parents where they denied important illnesses during childhood and the neonatal period. They reported having all the immunizations corresponding to the current Mexican vaccination card. They report having a seemingly normal intellectual development, currently in their 2nd year of high school. She has never been hospitalized and denies suffering from congenital anomalies and chronic degenerative diseases. Both parents and grandparents are from the same town, although they deny knowing consanguinity.
Her condition begins at 9-year-old, with difficulty seeing the class blackboard, which is the reason why she is taken to a consultation with an optometrist who diagnoses myopia of three diopters. From this moment, the graduation continuously increases by approximately one diopter annually; then, she goes to an ophthalmologist at the age of 16 year old, who diagnoses closed-angle glaucoma, which is treated with dorzolamide, timolol maleate, and brimonidine; in addition, a trabeculectomy is performed reducing IOP and improving vision.
At present, lens opacity is observed in biomicroscopy with slit lamp. See [Figure 1]. Visual acuity is 20/40 with spherical correctionof – 11 diopters in the left eye (LE) and – 12 diopters in the right eye (RE). IOP is taken with Goldman's tonometer, finding it at 27 mmHg in both eyes (BA). She refers chronic joint pain and stiffness in the ankles and wrist 3/10 on a Visual Analog Scale. Her height is 1.50 m and symmetrical brachydactyly is observed in both hands and feet.
|Figure 1: Slit-lamp biomicroscopy anterior segment image showing the narrow anterior chamber and pupil in mydriasis|
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The cardiac area is auscultated, detecting rhythmic beat and without additional noises. The rest of the interrogation and physical examination is normal.
In the fundus clinical picture, a wide papillary excavation in BA (9/10 RE and 8.5/10 in LE) with neuroretinal edge thinning in meridian X can be seen. It has nasal displacement in the origin of retinal vessels in BA. RA also presents tortuous veins in the path of temporal and nasal arches. LA has no vascular tortuosity. The hyperpigmented lesion is identified, not highlighted in BA. It is located at an intermediate point between the fovea and the papilla. The size is approximately 25 mm in diameter in BA. It is probably product of artifact since it is not identified in the image of the macular optical coherence tomography (OCT) [Figure 2] and [Figure 3].
Ultrabiomicroscopy was performed where the anterior chamber was found with shallow depth (RA: 1.14 mm and LA: 1.20), the iris insertion is anterior and high, causing obstruction of the iridocorneal angle, elongated ciliary body with dome appearance is observed. The lens is spherical with an anteroposterior diameter of 4.47 mm in BA and horizontal diameter of RA 6.70 mm and LA: 6.79 mm with a very anterior zonule insertion in the lens's equator [Figure 4].
In B mode ultrasound, there is a wide excavation of BA papilla. It appears the cystic image of aqueous content in LA that in the OCT is perceived as detachment of neurosensory retina located with respect to the pigmented epithelium. Macula with normal characteristics is seen.
Humphrey automated static campimetry was performed SITA strategy standard white on white reliable. A tubular visual field was documented in RA, which only irregularly respects the 5 paracentral degrees in the inferotemporal quadrant. In LA, an absolute scotoma of almost the entire upper hemisphere was found, which only respects the central 5° above the temporal superior quadrant.
Analysis with IOLMaster 700 with SWEPT Source (Zeiss®) Oberkochen, Zeiss State: Baden-Württemberg, Germany)provide an image where spherical crystalline and high internal density is observed See [Figure 5] and the values summarized in [Table 1] and [Table 2].
|Table 1: Values obtained by IOLMaster 700 with SWEPT Source (Zeiss®) for the right eye|
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|Table 2: Values obtained by IOLMaster 700 with SWEPT source (Zeiss®) for the left eye|
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| Discussion|| |
There are no well-defined diagnostic criteria for WMS. The diagnosis of WMS is considered when they have the following findings: ocular abnormalities (microspherophakia and ectopia lentis), short stature, brachydactyly, and joint stiffness. All these anomalies were found in the patient described, making it a clinically compatible case with WMS. The average age of onset of ocular symptoms reported in the literature is 7.5 years, which is close to the beginning of our patient at 9 years old.
The height of our patient (1.50 m) coincides with the average reported in adult women with WMS that is 130–157 cm. Although through the clinic, the genetic inheritance of the WMS cannot be differentiated and the specific tests were not carried out, the case of our patient may be associated with inbreeding due to the families that have lived many generations in a small and isolated population.
The microsphere in which the lens assumes a spherical shape with an increased anteroposterior diameter and a reduced equatorial diameter is observed in 94% of WMS cases. It is common that the spherophakia by generating an abnormal increase in lens curvature, leads to greater refractive power and causes lenticular myopia, which explains the high degree of myopia observed in our patient, despite having an eye length little.
Glaucoma is the most serious complication of WMS. It is caused in most cases by pupillary block due to the forward movement of the lens. This is evidenced by the ultrabiomicroscopy of our patient, in which the narrow anterior chamber is reported. In addition, the anterior and high iris insertion worsens the obstruction of the iridocorneal angle. These findings correlate with the alterations in papillary excavation documented in the different studies performed on the patient and with the loss of visual field observed in the campimetry.
The typical findings of the biometrics of patients with WMS coincide with what was detected in our patient through the IOLMaster 700 with SWEPT Source (Zeiss®), reporting thicker corneas (RE: 553 μm LE: 557 μm), shallow anterior chamber (RE: 1.86 mm LE: 1.80 mm), and shorter axial length (RE: 22.06 mm LE: 21.86 mm). Other findings in biometrics include higher keratometry values and oblique astigmatism.
As for the cardiac abnormalities, these may or may not be present. The most common electrocardiogram (EKG) abnormality is prolonged Corrected QT Interval (QTc) (QTc > 0.46 s), which is detected in 50% of patients. This abnormality was not detected in the EKG performed on our patient. The most common echocardiographic abnormality is the mitral valve prolapse.
Most cases of WMS are not diagnosed, they are often treated as myopic eyes until serious complications such as secondary glaucoma and lens dislocation occur. The rate of glaucoma development in patients with WMS reaches 100% in the third and fourth decades. In addition, the rate of legal blindness in these patients reaches 30%; therefore, the importance of early diagnosis cannot be underestimated.
| Conclusions|| |
Closed-angle glaucoma in young patients is not always associated with hypermetropia. Patients with high myopia, without an increase in the axial length of the eye or pathological myopic changes in the retina, should be examined further to detect the microspherophakia early. In this age group, structural or developmental eye abnormalities must be intentionally sought.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2]