Clinical Guidance

Given the limited number of individuals with WMS in the literature, no genotype-phenotype correlations for ADAMTS10, ADAMTS17, FBN1, or LTBP2 have been identified.

Source: GeneReviews — "Weill-Marchesani Syndrome"

Penetrance

The penetrance in those with autosomal recessive and dominant WMS is thought to be 100%. Intrafamilial and interfamilial variable expressivity is observed in WMS.

Source: GeneReviews — "Weill-Marchesani Syndrome"

Diagnostic Criteria

No consensus clinical diagnostic criteria for Weill-Marchesani syndrome (WMS) have been published.

Suggestive Findings

WMS should be suspected in individuals with the following clinical and radiographic features.

Clinical features

• Eye anomalies including microspherophakia and ectopia lentis

• Short stature

• Brachydactyly

• Progressive joint stiffness

• Thickened skin

• Pseudomuscular build

• Cardiovascular defects (e.g., patent ductus arteriosus, pulmonary stenosis, thoracic aortic aneurysm, cervical artery dissection, prolonged QTc)

Radiographic features

• Shortened long tubular bones

• Delayed bone age

• Broad proximal phalanges

Establishing the Diagnosis

The diagnosis of WMS can be established in a proband with characteristic and/or by identification of biallelic pathogenic (or likely pathogenic) variants in AD...

Source: GeneReviews — "Weill-Marchesani Syndrome"

Differential Diagnosis

Ectopia Lentis

Ectopia lentis may occur in the conditions listed in . All, however, are clinically distinct from Weill-Marchesani syndrome (WMS).

Table 4.

Other Genes and Disorders Associated with Ectopia Lentis

Gene(s) | Disorder | MOI | Clinically Distinctive Features

AASS | Hyperlysinemia type I (OMIM 238700) | AR | Mild ID

ADAMTSL4

| Ectopia lentis et pupilae (OMIM 225200) | AR | Ectopic pupil, flat-appearing iris, cataracts

CBS | Classic homocystinuria1 | AR | • DD/ID

• Tall slender w/asthenic habitus ("marfanoid")

• Biochemical features1

• Thromboembolism

FBN1 | Marfan syndrome | AD | • Skeletal manifestations: bone overgrowth joint laxity; extremities disproportionately long for trunk size (dolichostenomelia)

Source: GeneReviews — "Weill-Marchesani Syndrome"

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease in an individual diagnosed with Weill-Marchesani syndrome (WMS), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 6. Recommended Evaluations Following Initial Diagnosis in Individuals with Weill-Marchesani Syndrome

Source: GeneReviews — "Weill-Marchesani Syndrome"

Clinical Guidance

Use of ophthalmic miotics and mydriatics should be avoided as they can induce pupillary block. Potential increased risk of WMS-related ocular complications associated with contact sports should be discussed with the ophthalmologist.

Source: GeneReviews — "Weill-Marchesani Syndrome"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Weill-Marchesani Syndrome"

Surveillance Guidelines

Table 8.

Recommended Surveillance for Individuals with Weill-Marchesani Syndrome

System/Concern | Evaluation | Frequency

Ophthalmology

| Ophthalmology exams for early detection removal of ectopic lens can help possibility of pupillary block glaucoma. | Annually

Growth

| Assessment of height

Joint stiffness

| Assessment of joint range of motion by orthopedist/physiotherapist

Cardiac

anomalies | • Echocardiogram for evidence of valvular stenosis, arterial narrowing, /or aneurysm

• Electrocardiography to evaluate QT interval

| Periodic if normal; otherwise, specific follow up according to cardiac defect

Source: GeneReviews — "Weill-Marchesani Syndrome"