Boards Study Group Week 4

The three major systmes affects by Marfan syndrome are:

• Ocular
• Craniofacial
• Skeletal
• Cardiovascular
• Pulmonary

The most common ocular feature of Marfan syndrome is:

• myopia
• ectopia lentis
• complete retinal detachment
• cataracts

Marfan syndrome is caused by pathogenic variants in which of the following genes?

• COL3A1
• COL5A1
• FBN1
• FBN2

A diagnosis of Marfan syndrome is established by the findings of:

• any pathogenic variant in FBN1
• pathogenic variant in FBN1 associated with aortic root enlargement only
• pathogenic variant in FBN1 associated with aortic root enlargement or ectopia lentis
• a Marfan-specific systemic score of ≥7

Pathogenic variants in FBN1 can also associate with which other disorders?

• Familial Ectopia Lentis
• Loeys-Dietz syndrome
• Congenital Contractural Arachnodactyly
• MASS syndrome (mitral valve prolapse, myopia, aortic enlargement, non-specific skin/skeletal findings)

What percentage of individuals diagnosed with Marfan syndrome have the disorder due to a de novo variant?

• 25%
• 50%
• 60%
• 100%

Which of the following is not a cranofacial feature of Marfan syndrome?

• high arched/narrow palate
• downslanting palpebral fissures
• hypertelorism
• micro/retrognathia

FBN1 encodes the protein, fibrilin-1. This protein is an important because:

• it helps to regulate the expresison of various collagen-producing genes
• it assists with nonsense-mediated decay for various collagen-producing genes
• it contributes to microfibril structure in both elastic and non-elastic tissues
• it helps sequester TGF-beta, a transformational growth factor

Why might someone with Marfan syndrome be prescribed beta-blockers?

• beta-blockers can reduce the rate of aortic root dilation
• beta-blockers can help protect the structural integrity of the eye
• beta-blockers are helpful for pain management
• beta-blockers can relax the blood vessels, reducing the risk of aneursym

What is included in the decsription of "Marfanoid habitus" (which presents only some features of Marfan syndrome)?

• longer limbs
• stretchy skin
• tall, thin build
• pectus deformity
• dilated aortic root
• blue sclera

The diagnosis of vascular Ehlers-Danlos syndrome (vEDS) can be established by finding pathogenic variants in which gene?

• COL2A1
• COL3A1
• COL5A1
• PLOD1

Diagnosis of vEDS can only be made via genetic testing.

• True
• False

How else can a diagnosis of vEDS be made?

• Brain MRI
• Echocardiogram to invesitage the aorta
• Abdominal ultrasound
• Skin biopsy

When death occurs within the first two decades of life for someone diagnosed with vEDS, the most common cause is:

• rupture of the intestines
• sudden cardiac death
• rupture of the aorta or associated arteries
• uterine ruptures

Which of the following is not considered major diagnostic criteria for vEDS?

• Intestinal rupture
• Hypermobility of joints
• Family history of vEDS
• Arterial aneurysms, dissection, or rupture

What percentage of people diagnosed with vEDS have a de novo variant?

• 25%
• 40%
• 50%
• 60%

Which of the following would be the least common management recommendation for an individuals with vEDS?

• treatment for ocular manifestations with a ophthalmologist
• advisement to seek medical attention in response to any sudden, unexplained pain
• frequent monitoring of blood pressure
• possible prescription of beta-blockers to reduce risk of aneurysm development

What would distinguish vEDS from classic EDS?

• vEDS does not involve soft, doughy skin
• vEDS does not involve thin, transluscent skin
• Classic EDS does not involve easy bruising
• Classic EDS does not involve atrophic scarring

What is the life expectancy for someone with vEDS?

• vEDS has no effect on life expectanct
• Life expectancy can vary too widely to say
• The life expectancy is on average less than 40 years
• The life expectancy is on average betwee 40 and 60 years

Which of the following is an important role of type III collagen (which is the gene-product of COL3A1)?

• It forms the basal lamina of epithelia tissue
• It provides tensile strenght to skin and ligaments
• It maintains integrity of blood vessels
• It provides structure to cartilage

Kyphoscoliotic Ehlers-Danlos (kEDS) is associated with pathogenic variants in:

• COL5A1
• PLOD1
• FKBP14
• FBN2

PLOD1-related kEDS and FKBP14-related kEDS can be distinguised by which of the following?

• hearing loss is not associated with PLOD1
• hearing loss is not associated with FKBP14
• hypotonia is not associated with PLOD1
• blue sclera is not associated with PLOD1

What even is kyphoscoliosis?

• deviation from typical spine curvature causing rounding of the lower back only
• deviation from typical spine curvature causing rounding of the upper back only
• deviation from typical spine curvature causing both sidewasy curvature and rounding of the lower back
• deviation from typical spine curvature causing both sideways curvature and rounding of the upper back

Which of the following is not a major clinical featuer of kEDS?

• significant motor delay
• congenital hypotonia
• kyphoscoliosis (congenital or early-onset)
• generalized joint hypermobility

What is the inheritance pattern for both PLOD1- and FKBP14-related kEDS?

• Autisomal dominant
• Autisomal recessive
• Mitochondrial
• X-linked

PLOD1-related kEDS is less common than FKBP14-related kEDS.

• True
• False

Which of the following is not considered minor criteria for both PLOD1- and FKBP14-related kEDS?

• downslanted palpebral fissures
• pectus deformity
• blue sclera
• rupture/aneurysm of medium-sized artery

Individuals with FKBP14- and PLOD1-related kEDS are at an increased risk for:

• aortic dissection
• gastrointestinal perforation
• respiratory complications
• ectopia lentis

Which of the following would be appropriate management recommendations concerning musculoskeletal features of kEDS?

• strengthen large muscle groups via swimming or physical therapy
• annual orthopedic assessment, at minimum
• strengthening of muscles adjacent to hypermobile joints via sports such as gymnastics or distance running
• possible surgical intervention in response to spine curvature

Which of the following would be least likely to support a diagnosis of kEDS?

• severe kyphosis
• muscle hypotonia in infancy
• easy bruising with no family history
• spinal cord compression due to scoliosis

What is the inheritance pattern of Leber hereditary optic neuropathy (LHON)?

• Autosomal dominant
• Autosomal recessive
• Mitochondrial
• X-linked

Individuals with pathogenic variants in FOXL2 are thought to have:

• Jervell and Lange-Nielsen syndrome
• Hermansky-Pudlak syndrome
• Pendred syndrome
• Blepharophimosis, ptosis, and epicanthus inversus (BPES)

Which of the following conditions are related to pathogenic variants in a collagen genes?

• Marfan syndrome
• Stickler syndrome
• vascular EDS
• kyphoscoliotic EDS
• classic EDS
• Beals syndrome
• Usher syndrome

Congenital Contractural Arachnodactyly is characterized by which of the following?

• arachnodactyly
• progressive kyphoscoliosis
• marfanoid habitus
• dilated aortic root

What is the inheritance pattern of Pendred syndrome?

• Autosomal dominant
• Autosomal recessive
• Mitochondrial
• X-linked

Which of the following can present with both hearing and visual impairment?

• Usher syndrome
• Waardenburg syndrome
• Treacher Collins syndrome
• Leber hereditary optic neuropathy (LHON)

Which of the following genes are known to associate with Classic EDS?

• COL5A1
• COL11A1
• COL2A1
• COL5A2
• COL3A1

Classic EDS and hypermobile EDS both involve:

• increased risk for intestinal perforation
• joint hypermobility
• atrophic scarring
• scoliosis

Waardenburg syndrome type 4 is caused by mutations in EDNRB, EDN3, or SOX10. This is an example of:

• clinical/allelic heterogeneity
• genetic/locus heterogeneity