As mentioned above, Marfan syndrome is generally not difficult to diagnose due to its physical, ocular and vascular specific signs, but the wide variation in its clinical presentation, especially in recessive Marfan syndrome, often causes diagnostic difficulties and controversies. Modern diagnostic criteria were established at the 7th International Congress of Human Genetics in 1986 and clearly defined at the first International Symposium on Marfan Syndrome in 1988, and in 1996, dePaepeA was re-amended to be considered as the unified criteria.
1.Specific content of the criteria
(1)Skeletal system
Main criteria: at least 4 of the following manifestations – chicken chest; funnel chest requiring surgical correction; reduced ratio of upper volume/lower volume, or ratio of upper limb span length/height greater than 1.05; positive wrist sign, finger sign; scoliosis greater than 20 degrees, or anterior displacement of the spine (scoliosis count); reduced abduction of the elbow joint (<170 degrees); mid-ankle middle joint dislocation forming a flat foot; any degree of, acetabular pronation (iliac joint entropion) (determined on X-ray).
Secondary criteria: moderate funnel chest: abnormally enhanced joint movement; high palatal arch with crowded overlapping teeth; facial features: long head – normal cephalic index of 75.9 or less, zygomatic hypoplasia, intraocular sunken eyes, reduced jaw, and downsloping lid fissures. Conditions to be met for skeletal system involvement: at least two primary criteria or one primary plus two secondary criteria.
(2) Ocular system
Primary criteria: dislocation of the lens.
Secondary criteria: abnormally flattened cornea (measured by keratometer); increased axial length of the eye (measured by ultrasound); hypoplasia of the iris or ciliary muscle resulting in pupillary constriction. Ocular system involvement is subject to criteria: primary criteria or at least two secondary criteria.
(3) Cardiovascular system
Primary criteria: dilated ascending aorta with or without aortic regurgitation and at least a dilated Valsava’s sinus; ascending aortic coarctation.
Secondary criteria: mitral valve prolapse with or without mitral regurgitation; dilated main pulmonary artery (in the absence of valvular or peripheral pulmonary stenosis and other obvious causes, and less than 40 years of age); calcified mitral annulus (less than 40 years of age); dilated or entrapped descending or abdominal aorta (less than 50 years of age).
Conditions to be met for cardiovascular involvement: one major criterion or one minor criterion is sufficient.
(4) Pulmonary system
Major criterion: none.
Secondary criteria: spontaneous pneumothorax; apical pulmonary alveoli (confirmed by chest radiograph).
The pulmonary system is considered to be involved if one of these is present.
(5) Skin and body envelope
Primary criteria: none.
Secondary criteria: skin atrophy (stretched marks), not associated with significant overweight, pregnancy or repeated compression; recurrent hernia or incisional hernia.
The presence of one secondary criterion is considered skin or body envelope involvement.
(6) Dural (spinal) meninges
Primary criteria: CT or MRI finding of dural bulge.
Secondary criteria: none.
(7) Family or genetic history
Primary criteria: one parent, child, or sibling meets this diagnostic criterion; presence of a known mutation in the FBNI gene that causes Marfan syndrome; presence of a known haplotype of the FBNI gene that is identical to that of a patient with Marfan syndrome in his or her family.
Secondary criteria: none.
Due to the significance of family or genetic history in the diagnosis, one of the primary criteria must be present.
2. Prerequisites for the diagnosis of Marfan syndrome
For specific cases: If there is no family or genetic history, at least two different systems of don’t criteria and one-third organ involvement are required; if a mutation in a known Marfan syndrome gene is detected, a system with one major criterion and a second system involvement is diagnostic.
For family members of specific cases: one major criterion in the family history, one major criterion in one system, and a second systemic involvement are sufficient for diagnosis.