Weill-Marchesani

BASICS


DESCRIPTION


• A rare connective tissue disorder associated with short stature, brachydactyly (short digits), joint stiffness, and eye anomalies.


– Intraocular abnormalities include microspherophakia, ectopia lentis, glaucoma, and lenticular myopia


EPIDEMIOLOGY


Prevalence


• Not well documented


– Listed as a “rare” disease by the Office of Rare Diseases (ORD) of the National Institutes of Health (occurs in<200,000 people in the US)


RISK FACTORS


Family history


Genetics


• Autosomal dominant and recessive inheritance have been described.


– Fibrillin-1 mutations on chromosome 15q21 have been reported with autosomal dominant transmission (1)[C].


ADAMTS10 mutations on chromosome 19p are present in families with autosomal recessive inheritance (2)[C].


GENERAL PREVENTION


Genetic counseling to inform family planning


PATHOPHYSIOLOGY


• Mesodermal dysgenesis causes extremely long and loose zonules, which give rise to lens-related complications (3)[C] including the following:


– Lenticular myopia from a globular lens


– Pupillary block as the lens moves forward and contacts the iris


– Secondary iris bombe and anterior chamber shallowing lead to angle-closure glaucoma.


– Ectopia lentis from zonular dehiscence can lead to luxation into anterior chamber.


ETIOLOGY


Extracellular matrix proteins important in the development of the lens, skin, and heart are dysfunctional.


DIAGNOSIS


HISTORY


A family history of Weill–Marchesani syndrome or manifestations of the syndrome


PHYSICAL EXAM


• Microspherophakia and brachydactyly must be present (4)[C].


– Other features suggesting Weill–Marchesani syndrome include joint restriction and short stature.


– Cardiac anomalies can be associated with this condition such as patent ductus arteriosus, mitral and aortic valve stenosis, prolonged QTc, and mitral valve prolapse.


DIAGNOSTIC TESTS & INTERPRETATION


Lab


Initial lab tests

Molecular genetic testing is available for ADAMTS10.


Follow-Up & Special Considerations

Consider consultation with medical geneticist.


Imaging


Initial approach

• Cardiac echocardiogram and EKG


• Consider plain films of digits/joints


Follow-up & special considerations

Consider cardiology consult especially if echo/EKG is abnormal.


Pathological Findings


Zonules are long and loose due to mesodermal dysgenesis often leading to dehiscence.


DIFFERENTIAL DIAGNOSIS


Subluxed lens


• Marfan syndrome


• Homocystinuria


• Sulfite oxidase deficiency


• Hyperlysinemia


• Simple dominant ectopia lentis


• Ectopia lentis et pupillae


• Glaucoma-lens ectopia–microspherophakia–stiffness–shortness (GEMSS) syndrome


• Klinefelter syndrome


• Mandibulofacial dysostosis


• Alport syndrome


• Trauma


• Buphthalmos


• Aniridia


• Familial ectopia lentis


• Persistent fetal vasculature


• Coloboma


• Syphilis


• Xanthine oxidase deficiency


• Molybdenum cofactor deficiency


• Hyperlysinemia


• Methylenetetrahydrofolate reductase deficiency


TREATMENT


MEDICATION


Medical treatment of pupillary block glaucoma is difficult due to the unpredictable effects of miotic and mydriatic agents.



ALERT


• Use of miotic agents can induce pupillary block glaucoma in patients with microspherophakia and intact lens (3)


• There are reports of angle closure with the use of mydriatics such as cyclopentolate (5)


• Intraocular pressure can be controlled using topical beta-blockers, alpha-2 agonists, carbonic anhydrase inhibitors, and prostaglandins.


– Lowering of intraocular pressure in the pediatric population is first achieved through the use of topical beta-blockers such as timolol. If monotherapy is insufficient, these medications can be combined with carbonic anhydrase inhibitors such as dorzolamide. Alpha-2 agonists such as brimonidine are contraindicated in children younger than 2 years due to serious side effects (i.e., lethargy, sleepiness). Prostaglandins such as latanoprost are less effective in children.

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Nov 9, 2016 | Posted by in OPHTHALMOLOGY | Comments Off on Weill-Marchesani
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