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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