Connective Tissue Disorders

Question 1

LOEYS-DIETZ SYNDROME

Answer 1

vascular findings

(cerebral, thoracic, and abdominal arterial aneurysms and/or dissections) and skeletal manifestations (pectus excavatumor pectus carinatum, scoliosis, joint laxity, arachnodactyly, talipes equinovarus- club foot points down ward and inward)

• 75% have LDS type I with craniofacial manifestations (ocular hypertelorism, bifid uvula/cleft palate, craniosynostosis);
• 25% have LDS type II with cutaneous manifestations (velvety and translucent skin; easy bruising; widened, atrophic scars).

Question 2

EHLERS-DANLOS SYNDROME, VASCULAR TYPE (Type IV)

Answer 2

cDNA or genomic DNA COL3A1 sequence analysis (98-99%)

Major criteria: arterial rupture, intestinal rupture, uterine rupture during pregnancy, FH of Vascular EDS.

Minor criteria: thin, translucent skin, easy bruising, thin lips and philtrum, small chin, thin nose, large eyes, aged appearance of hands, small joint hypermobility, tendon/muscle rupture, varicose veins, AV carotid-cavernous sinus fistula, pneumothorax, CHD, clubfoot, gum recession

Question 3

EHLERS-DANLOS SYNDROME, KYPHOSCOLIOTIC TYPE (Type VI)

Answer 3

Responsible gene: PLOD1 (AR)

Cytogenetic locus: 1p36.3-p36.2

Major features: friable, hyperextensible skin, thin scars, easy bruising, generalized joint laxity, severe muscle hypotonia, progressive scoliosis, scleral fragility, and rupture of the globe.

Question 4

EHLERS-DANLOS SYNDROME, KYPHOSCOLIOTIC TYPE (Type VI)

Answer 4

Clinical Tests:

Crosslinked telopeptides are excreted in urine as a byproduct of increased collagen turnover.

Inc ratio of deoxypyridinoline/ pyridinoline by urine HPLC is highly sensitive and specific. Enzyme activity in cultured fibroblasts (<25% activity is abnormal)

Question 5

Clinical Features and Diagnostic Criteria Marfan

Answer 5

Major involvement of 2 body systems and minor involvement of a 3rd.

Major Criteria

• CV: Dilation or dissection of the ascending aorta
• Skeletal: pectus carinatumor excavatum, reduced upper:lower segment or arm span:ht, scoliosis, pes planus, high palate, reduced elbow extension, protrusioacetabulae,
• Eye: ectopia lentis,
• Dura: lumbosacral duralectasia, FH: pathogenic FBN1mutation, 1stdegree relative with Marfan syndrome.

Minor Criteria

• CV: MV, MR, dilation of main PA, mitral annulus calcification, dilation or dissection of the descending thoracic or abdominal aorta ate age <50yrs,
• Skeletal: moderate pectus excavatum, joint hypermobility, high palate with crowding of teeth, typical facial features
• Eye: flat cornea, increased length of globe, decreased pupillary miosis,
• Lung: pneumothorax, apical lung blebs,
• Skin: skin striae, hernia

Question 6

Marfan Gene

Answer 6

Fibrillin 1

Question 7

CONGENITAL CONTRACTURAL
ARACHNODACTYLY (Beals Syndrome)

Answer 7

• Fibrillin-2
• Marfanoid appearance, long slender fingers and toes, crumpled ears, major joint contracture, muscle hypoplasia, kyphosis/scoliosis,
• Severe/lethal: aortic dilation, ASD, VSD, IAA, duodenal or esophageal atresia, malrotation

Question 8

Loeys Dietz

Answer 8

arterial tortuosity,

hypertelorism

bifid uvula ± cleft palate

Question 9

Loeys Dietz

Answer 9

• tendency for more aggressive aortic dissection (including in normally sized vessels),
• extra-aortic vascular involvement and a wide
• phenotypic expression including individuals lacking the originally described clinical features of the syndrome.
• Pregnant women with LDS are at higher risk of aortic aneurysms and uterine rupture.