Genetics: Pectus Innovations

In pectus excavatum clinics, genetic evaluation primarily screens for Marfan syndrome and Ehlers-Danlos syndrome.

Marfan syndrome skeletal evaluation includes the wrist sign (thumb and pinky finger overlap when wrapped around wrist) and thumb protrusion past the ulnar border, assessing for long bone overgrowth relative to trunk.

Marfan syndrome skeletal findings include evaluation of arm span to height ratios and upper to lower segment ratios.

Additional Marfan skeletal findings include pectus excavatum, pectus carinatum, scoliosis, and hind foot deformities.

Marfan syndrome screening is motivated by cardiac risk (aortic dissection) and other complications including mitral valve prolapse and retinal detachments.

Marfan syndrome diagnosis now centers on cardiac findings, with echocardiogram or MRI as main tools to evaluate for dilated aortic root.

Marfan evaluation includes assessment for lens dislocations, and in suggestive cases, genetic testing of the fibrillin gene.

Patients with Marfan-like characteristics may warrant extended genetic evaluation for other syndromes involving TGF beta signaling, which contributes to aortic remodeling and long bone overgrowth.

Ehlers-Danlos syndrome is by far the more common condition evaluated in pectus clinics compared to Marfan syndrome.

Ehlers-Danlos syndrome represents a grouping of related connective tissue conditions, not a single entity.

Classic Ehlers-Danlos is caused by defects in collagen 5 and characterized by joint hypermobility and abnormal skin that is fragile, thin, with weak papery scars.

Vascular Ehlers-Danlos is caused by mutations in collagen 3 and involves internal organ fragility rather than primarily hypermobile joints.

Vascular Ehlers-Danlos is one of the least common conditions seen in pectus clinics.

Vascular Ehlers-Danlos screening focuses on family or personal history of ruptures (bowel, aortic, or uterine rupture).

Vascular Ehlers-Danlos has genetic testing that is 99% sensitive.

Hypermobile Ehlers-Danlos is the type typically evaluated in pectus clinics, characterized by very flexible patients.

The Beighton score is a formal test of 9 different joints, scored 1 point for each side except the hips, used to assess hypermobility.

Beighton score criteria include: arm hyperextension past 10 degrees, pinky hyperextension past 90 degrees, thumb apposition to forearm, knee hyperextension past 10 degrees (all bilateral, 8 points total), and placing hands flat on floor without bending knees (assessing hip hypermobility).

A Beighton score of 5 or more hypermobile joints meets criteria for generalized hypermobility.

Additional hypermobile Ehlers-Danlos findings include mild skin changes (mildly hyperextensible, easy bruising, scarring abnormalities, striae) and family history of hypermobility.

The dividing line between being flexible and having Ehlers-Danlos may be very fuzzy; diagnosis requires similar findings in family members and presence of clinical problems.

Hypermobile Ehlers-Danlos patients exhibit a constellation of findings: chronic pain, chronic headaches/migraines, TMJ dysfunction, easy bruising/bleeding, orthostatic hypotension/dizziness/blacking out with standing, episodes of racing heartbeat, chronic constipation with IBS, panic and anxiety disorders, and sleeping problems.

Most adult hypermobile Ehlers-Danlos patients presenting to clinic have almost all of the associated constellation of problems.

In children with hypermobile Ehlers-Danlos, problems may be very mild or not evident initially, but may emerge during puberty, which may coincide with consideration of pectus surgery.

The chronic pain aspect of hypermobile Ehlers-Danlos can influence risk for more pain from pectus surgery.

Hypermobility is a risk factor for fibromyalgia; 50% of teenagers diagnosed with fibromyalgia have hypermobility.

Fibromyalgia involves central sensitivity to pain, meaning patients are unable to filter out unwanted pain signals in the same way as other persons.

Hypermobile patients may be at risk for more problems with chronic pain due to central pain sensitivity mechanisms.

One clinician's screening approach for pectus patients includes checking for double-jointedness, Marfan appearance (arachnodactyly), and striae, with genetics referral if findings are present.