Weill-Marchesani syndrome

The estimated prevalence is 1/100,000.

Weill-Marchesani syndrome is inherited in either an autosomal recessive or an autosomal dominant manner, depending on the underlying gene. In the autosomal recessive form (ADAMTS10, ADAMTS17, LTBP2), the recurrence risk for siblings of an affected proband is 25%; in the autosomal dominant form (FBN1), each child of an affected individual has a 50% risk of inheriting the pathogenic variant.

No consensus clinical diagnostic criteria have been established for Weill-Marchesani syndrome. The clinical suspicion is raised by the combination of microspherophakia with ectopia lentis, short stature, brachydactyly, and progressive joint stiffness, supported by ophthalmological examination (slit-lamp assessment of the lens, gonioscopy, intraocular pressure measurement) and cardiological evaluation (echocardiography and electrocardiography). The diagnosis is confirmed by molecular genetic testing.

Main differential diagnoses include:

• : shares short stature, brachydactyly, stiff joints, delayed bone age, thickened skin, and cardiac disease; distinguished by hepatomegaly and the absence of lens abnormalities
• Acromicric dysplasia: shares short stature, brachydactyly, stiff joints, delayed bone age, cone-shaped phalangeal epiphyses, thickened skin, and cardiac disease; distinguished by the absence of lens abnormalities
• : shares ectopia lentis and cardiovascular involvement; distinguished by tall stature with bone overgrowth, joint laxity, dolichostenomelia, and aortic root dilatation (the opposite habitus to Weill-Marchesani syndrome)

• Establishing the diagnosis: molecular genetic testing confirms the diagnosis and provides the basis for genetic counselling of the affected individual and their family.
• Specific and individualised surveillance: molecular confirmation of the diagnosis can support regular ophthalmologic follow-up for lens abnormalities and glaucoma, as well as cardiologic follow-up, including echocardiography and electrocardiography. Annual assessment of height and joint range of motion may also be considered.
• Family member testing: once the familial pathogenic variant is known, predictive testing of at-risk relatives can clarify their genetic status and inform individual medical care.

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