Meester-Loeys syndrome

Due to insufficient data, no reliable statement on prevalence can currently be made.

Meester-Loeys syndrome is inherited in an X-linked recessive manner. Female carriers transmit the BGN variant to 50% of their offspring of either sex. Affected males transmit the variant to all daughters and to no sons. Prenatal molecular testing is technically possible once the familial pathogenic variant has been identified.

There are no established clinical diagnostic criteria, biochemical markers, or specific imaging findings for Meester-Loeys syndrome; the diagnosis is primarily established by identification of a pathogenic variant in BGN through molecular genetic testing. Clinical evaluation typically prompts molecular testing when thoracic aortic aneurysm or dissection occurs together with skeletal, craniofacial, or cutaneous features suggestive of a syndromic connective-tissue disorder, particularly in male individuals.

Main differential diagnoses include:

• : ectopia lentis, marfanoid skeletal habitus, autosomal-dominant aortic-root dilatation; FBN1.
• : autosomal-dominant or autosomal-recessive arterial tortuosity and aneurysms, hypertelorism, bifid uvula, cervical-spine instability; TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3, SMAD2, IPO8.
• Vascular : autosomal-dominant arterial, intestinal and uterine fragility, thin translucent skin; COL3A1.

• Confirming the suspected clinical diagnosis through identification of the causative pathogenic variant in the affected individual.
• Providing the molecular basis for specific and individualised surveillance and clinical management; a confirmed molecular diagnosis is a prerequisite for targeted medical care decided by the treating physicians in consultation with the affected individual.
• Enabling predictive testing of at-risk relatives so that variant carriers can be identified before symptoms appear and can be offered appropriate clinical follow-up.

• Milewicz DM, Cecchi AC. Heritable thoracic aortic disease overview. 2003 Feb 13 [updated 2023 May 4]. In: Adam MP, Bick S, Mirzaa GM, et al., editors. GeneReviews^® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. PMID: .
• Meester JAN, Hebert A, Bastiaansen M, Rabaut L, Bastianen J, Boeckx N, et al. Expanding the clinical spectrum of biglycan-related Meester-Loeys syndrome. NPJ Genom Med. 2024;9(1):22. PMID: .
• Meester JAN, De Kinderen P, Verstraeten A, Loeys B. Meester-Loeys syndrome. Adv Exp Med Biol. 2021;1348:265-272. PMID: .