Thread by @KirtanPatolia

The spectrum of Marfan syndrome and related connective tissue disorders is intriguing and mind-bending 💫✨

Here is a🧵exploring it

@CPSolvers @rabihmgeha @DxRxEdu @Sharminzi @AnnKumfer @rav7ks @sargsyanz @DrCindyCooper @jackpenner @MatthewHoMD @ASanchez_PS

#MedTwitter

#2 Skeletal manifestations

-Tall stature
-Long slender arms & legs
-Arachnodactyly
-Pectus excavatum
- Pectus carinatum
-Joint hypermobility
-Pes planus
-Camptodactyly (bent fingers)
-Kyphoscoliosis
-Micrognathia & Retrognathia
-Dolichocephaly
-Malar hypoplasia

#MedTwitter

#3 Cardiovascular

-Mitral valve prolapse (can lead to CHF & arrhythmias)
-Aortic aneurysms
-Aortic root dilation
-Aortic dissection
-Aortic regurgitation
-Pulmonary artery dilation (often asymptomatic)

#MedTwitter #CardioTwitter @Gurleen_Kaur96 @KannuBansalMD @this_is_svenka

#4 Ocular manifestations

- Lens dislocation/Ectopia lentis (usually bilateral and superotemporal)
- High Myopia/Astigmatism
- Iridodenesis
- Abnormally flat cornea
- Cataracts
- Glaucoma
- Retinal detachment
- Hypoplastic iris

@DGlaucomflecken #ophthalmology #MedTwitter

#5 Pulmonary manifestations

- Apical pulmonary blebs
- Spontaneous pneumothorax

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#6 Neurologic manifestations

- Dural leak and ectasia leading to spontaneous intracranial hypotension (orthostatic and thunderclap headache with smooth diffuse meningeal enhancement)
-Stroke
-Spinal stroke
-Subdural hematoma
- Subarachnoid hemorrhage

#NeuroTwitter @caseyalbin

Differential #1 MASS phenotype (fibrillin-1 gene)

-myopia
-mitral valve prolapse
-mild aortic enlargement
- nonspecific skin and skeletal features

#MedTwitter #genetics

Differential #2 Homocystinuria (Cystathionine beta-synthase deficiency/CBS)

- Ectopia lentis (CBS deficiency->low cysteine->low cysteine in zonular fibres->lens dislocation)
- Intellectual disability
- Hypercoagulability
- Vascular events (Stroke, MI)
- Osteoporosis

#MedTwitter

Differential #3 Ehlers Danlos syndrome variants (collagen gene)

-Hypermobile
-Classical
-Vascular (Carotid-cavernous fistula, Cervical dissection, SAH, ICH, organ rupture)
-Kyphoscoliosis
-Arthrochalsia
-Dermatosparaxis (sagging skin)
-Spondylodysplastic
-Myopathic

#genetics

Differential #4 Loeys-Dietz (TGF-beta and SMAD)

-Vascular tortuosity & aneurysms
-Bifid uvula
-Exotropia
-Hypertelorism
-Cervical spine instability
-Hydrocephalus
-Eosinophilic esophagitis
-IBD like features

#genetics #MedTwitter #RareDisease

Differential #5 Beals syndrome (fibrillin-2 gene)

-Congenital contractural arachnodactyly
-Fixed contractures of joints
-Crumpled pinnae
-Club foot

#genetics #MedTwitter #RareDisease

Differential #6 Shprintzen-Goldberg syndrome (SKI gene and TGF-beta)

-Craniosynostosis
-Dural ectasia (nerve compression)
-Hypertelorism

#RareDisease

Differential #7 Familial thoracic aortic aneurysm and dissection (ACTA2 and TGF-beta mutations)

-Livedo reticularis
-Iris floculi

#genetics #RareDisease

Differential #8 Weill-marchesani syndrome (ADAMTS10 and ADAMTS17)

-ectopia lentis
-microspherophakia
-severe myopia
-glaucoma
- short stature
-joint stiffness
-brachydactyly

#genetics #RareDisease

Differential #9 Stickler syndrome (Collagen gene mutations)

-myopia
-Retinal holes
-Retinal detachment
-Sensorineural hearing loss

#10 Cutis laxa (fibrillin 4)

#11 Stiff skin syndrome & Geleophysic and
acrophysic dysplasia (fibrillin 1)

#12 Arterial tortuosity syndrome

#13 Pseudoxanthoma elasticum (ABCC6)

Finally associations at molecular levels

#14 filamin A & eIF2alpha kinase 4 mutations

-pulmonary capillary hemangiomatosis
-PVOD
-alveolar dysplasia
-periventricular nodular heterotopia
-valvular defects
-ILD
-Coagulopathy

#MedTwitter #RareDisease

#15 TGF beta -> TGF-beta receptor-> BMP/BMPR-> SMAD4/3 pathway

- Hereditary hemorrhagic telangiectasia & juvenile polyposis (SMAD4, endoglin, ACRVL1, BMP9)
-Pulmonary HTN
-Colorectal neoplasms
-Fibrodysplasia muscular ossificans

#MedTwitter #genetics #RareDisease

Thank you for reading.

Any suggestions appreciated

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