Marfans Syndrome Examination (seated) Overall Tall, disproportionately long limbs compared to trunk Upper Limbs Arachnodactyly, thumb

mb sign, wrist sign(overlap > 1cm) collapsing pulse reduced extension of elbows Face Dolichocephalic(long-headed) Blue sclera, iridodonesis, myopia, ectopia lentis (superolateral) High arched palate Meishers elastoma No thyroidectomy scar Chest Pectus excavatum or carinatum Thoractomy scar (Hx of repair of aortic aneurysm) No gynaecomastia LL Arachnodactyly Stand up Kyphoscoliosis Abdomen: inguinal or femoral herniae, hernia scars, striae atrophicae Genu recurvatum Pes planus Request Cardiovascular examination: MVP, AR Respiratory: scar suggestive of chest tube for pneumothorax, pleurodesis Lower limbs for weakness and numbness (complications of dural ectasia) Measure his arm span to height ratio (>1) Measure pubis-sole to pubis-vertex ratio (>1) Presentation Sir, this patient has Marfans syndrome as evidenced by tall stature with disproportinately long limbs (also known as dolichostenomilia). He has got arachnodactyly with hyperextensible joints with positive thumb sign (Steinberg), wrist sign (Walker), hyperextension of the elbows and genu recurvatum and pes planus. There is presence of dolicocephaly, with iridodenesis, blue sclera and is myopic. He has a high arched palate. I did not detect any Meishers elastoma (small papules of the skin of the neck). There is also kyphoscoliosis with pectus excavatum. Of note there are chest wall scars suggestive of previous chest tube insertions. There is no obvious inguinal or femoral hernia, scars or striae atrophicae.

There is no collapsing pulse. I did not detect any evidence of malar rash or calve swelling suggestive of a DVT which are features of homocystinuria. There is also no neck scars, mucosal neuromas or hyperpigmentation to suggest MEN type 2B as these patients have a marfanoid habitus. There is also no gynaecomastia or eunuchoid habitus to suggest Klinfelters syndrome (say this if patient is a man). I would like to complete my examination by measuring his arm span to height ratio as well as his sole-pubis to pubis-vertex ratio; in addition I would like to perform a cardiovascular examination to look for MVP, AR; a respiratory examination for plurodesis, as well as lower limb examination for weakness or numbness secondary to dural ectasia. Questions What are the differential diagnoses for a patient who has a tall stature? Marfans syndrome Homocystinuria Malar flush, mental retardation, inferomedial ectopia lentis Hx of epilepsy, IHD(CABG scar), DVT, osteoporosis Presence of homocystine in the urine via cyanide-nitroprusside test Autosomal recessive inborn error of metabolism of amino acid with deficiency of cystathionine beta synthetase MEN type 2b Hyperpigmentation, mucosal neuromas(lips, tongue, palate, conjunctiva and cornea), proximal myopathy MEN 1: Pituitary, parathyroid, pancreatic (PPP) MEN 2a: Parathyroid, adrenals(phaechromocytoma), thyroid (MTC) (PAT) MEN 2b: PAT and hyperpigmentation, mucosal neuromas, marfanoid Klinefelters syndrome Male patient, eunuchoid habitus (arm span> height, sole-pubis>pubis vertex, femenine fat distribution Gynaecomastia, lack of beard and axillary hair, voice is not masculine, pea-sized testes (normal >3.5cm), varicose veins Mentally subnormally, infertile Rule out hypo-osmia for Kallmans syndrome (idiopathic hypogonadotrpic hypogonadism with hypo-osmia, cleft palate/lip, congenital deafness or blindness which can be treated with gonadotropins and GnRH for fertility) Raised FSH and estradiol with low testosterone and chromosomal analysis 47XXY(buccal smear for karyotyping) Infertile as majority are 47XXY (80%) and others can be due to more than 2 X or > 1Y or mosaicism (can be fertile) Most common cause of male hypogonadism, 1:500 Increased risk of DM, Br cancer and SLE Increases with increasing maternal or paternal age

What is Marfans syndrome? It is an inherited autosomal dominant connective tissue disorder Affecting the skeletal system, cardiovascular system with ocular abnormalities 1 in 15 000 Male=Female What is the mode of transmission of Marfans syndrome? Autosomal dominant Chromosome 15q21 Defects in fibrillin gene How is Marfans syndrome diagnosed? Based on the Ghent criteria which takes into account o Family history o Molecular studies o 6 organ systems Skeletal Skin Eye CVS Pulmonary Dura (dura ectasia) What are the ocular features of Marfans syndrome? Small spherical lens Cataracts Lens subluxation Glaucoma Hypoplasia of dilator pupillae, therfore difficulty with pupillary dilatation Flat cornea Myopia Retinal detachment Increased axial length of the globe How would you investigate? Molecular studies Annual echocardiography Monitor aortic diameter (normal <40mm, composite graft required if >50mm) MV function Ophthalmic examination How would you manage? Education and psychological counselling Annual cardio review Beta-blockade (retards rate of aortic root dilatation)

Aortic root graft >50mm IE prophylaxis Eye review

What is the prognosis? Death due to cardiovascular complications Aortic dissection CCF secondary to AR Life span is about mid forties What are the complications of pregnancy in Marfans syndrome? Early premature abortion Death from aortic dissection (safe if aortic root<40mm) How would you counsel patient? Affected individuals can transmit the condition to 50% of their offspring. The recurrence risk is 50% if 1 parent is affected. The recurrence risk is small if neither parent is affected. During counseling, the variability of the disease should be emphasized, as an affected child may be more or less affected than the parent. How do you assess hypermobility? Beightons 9 point scale passive dorsiflexion of the little finger beyond 90 passive apposition of the thumb to the flexor aspects of the forearm hyperextension of the elbow beyond 10 hyperextension of the knee beyond 10 forward flexion of the trunk, with the knees straight, so the palms of the hands rested easily on the floor If 4 or more => Joint laxity What are the causes for hypermobile joints? Benign Joint Hypermobility Syndrome (Majority) Ehlers Danlos Syndrome Marfans syndrome Osteogenesis Imperfecta What are the causes of blue sclera? Marfans syndrome Ehlers Danlos Syndrome Osteogenesis Imperfecta Pseudoxanthoma elasticum Chronic steroid intake