CME INDIA Case Presentation by Dr. S. S. Lakshmanan, MD, (Gen Medicine), FRCP(GLASG), FICP, FIMSA, DNB Senior Consultant Internal Medicine & Diabetologist, Priya Nursing Home, Chennai.

CME INDIA Case Study

Diagnose a unique case - 17-year-old boy with wheezing, cough and haemoptysis.

17-year-old boy got admitted with wheezing and cough with haemoptysis for 5 days. He has a similar history for 5 years.

CME INDIA Discussion (21/04/2022)

 Dr. Atri Gangopadhyay, Pulmonologist, Ranchi:

  • Young boy recurring haemoptysis.
  • Possible differentials.
  • Childhood bronchiectasis.
  • Look for clubbing.
  • Respiratory allergy, coughing bouts cause haemoptysis.
  • Vasculitis.
  • Go for urine RE, KFT.
  • If suspicious, Then CTD profile.
  • Helminthiasis.

Dr. D. P. Khaitan, Consultant Physician Gaya:

  • If there is suspicion of childhood. bronchiectasis, one should also look for splenomegaly and albumin in urine due to associated secondary amyloidosis specially in long standing cases.
  • Bronchiectasis.

Dr. Nishith Kumar, Pulmonologist, Ranchi:

  • Kindly get HRCT thorax Done. Check Absolute Eosinophil Count.
  • Send Total Serum IgE & Serum IgE specific for Aspergillus Fumigatus,
  • ANCA Screen.
  • Do send sputum for AFB & MTB CBNAAT.
  • H/O Bronchial Asthma like illness + radiological picture consistent with that of cystic bronchiectasis.
  • If H/O off & on Haemoptysis/recurrent exacerbation do think of ABPA-CB (Allergic Bronchopulmonary Aspergillosis- Central Bronchiectasis).
  • Do evaluate IgG, IgM, IgG levels if initial evaluation is negative for ABPA & vasculitis.

Dr. S. S. Lakshmanan, MD, FRCP, GLASG, DNB:

  • Posting his CT chest
  • Gene Xpert sputum negative
  • Can you connect the diagnosis?
  • Hint- Collagen
Diagnose a unique case - 17-year-old boy with wheezing, cough and haemoptysis.
Diagnose a unique case - 17-year-old boy with wheezing, cough and haemoptysis.

Dr. Nishith Kumar Pulmonologist, Ranchi:

  • I can appreciate cystic bronchiectasis changes in the given film along with other features as mentioned in the report.
  • Consider to get Total Serum IgE, Aspergillus Specific IgE as advised…
  • In case ABPA workup comes negative. Proceed with other investigations as advised priorly. Rarely chronic bronchiectasis may present with secondary infections like NTM/Nocardiosis etc which may warrant BAL.

Dr S. S. Lakshmanan, MD, FRCP, GLASG, DNB:

  • Please see these pics:
Diagnose a unique case - 17-year-old boy with wheezing, cough and haemoptysis.

Dr. Balajee, Pulmonologist Pondicherry:

  • Marfans

Dr. Arun Kedia, Diabetologist, Raipur:

  • Marfans

Dr. Kiran Shah MD Physician, Vadodara:

  • Wrist sign, Marfan Syndrome

Dr. S. S. Lakshmanan, MD, FRCP, GLASG, DNB:

Other characteristics associated with this patient: Height 168 cm. Arm span 174 cm

  • It is a case of Marfan with lung involvement
  • D/D Vascular Ehlers Danlos.
  • In vED also lung involvement described
  • ECHO MVPS is present

Dr. Varun Kumar, DM Card., Sante Vita Hosp., Ranchi:

  • Spontaneous pneumothorax is more common in Marfan’s.

Dr. Nishith Kumar, Pulmonologist, Ranchi:

  • Spontaneous Pneumothorax is definitely the typical presentation. bronchiectasis is not that uncommon.
  • Bronchiectasis is a well-established risk factor for non-tuberculous mycobacteria (NTM) lung disease.
  • Still NTM along with other infections needs to be ruled out as these patients are prone to develop secondary infection.
  • Nice case👌🏻

ECG of the case

Interpretation by Dr. D. P. Khaitan, Sr consultant physician, Gaya:

Diagnose a unique case - 17-year-old boy with wheezing, cough and haemoptysis.

Findings on ECG:

  • Heart rate = 94 bpm.
  • A reverse Δ sign present either over the descending QRS limbs or appearing just immediately after the QRS transforming the ST segment with somewhat dipped appearance (please see in inferior leads II, III and aVF).
  • T wave mostly upright except in aVL, V1-2 but within normal limits.
  • R in V5 more than 26 mm with q over V5-6 with up T = left ventricular hypertrophy with diastolic overload.
  • P terminale in V2 with negative component > 0.04 sec = ? left atrial enlargement.
  • Spodick sign + throughout (obvious on zooming the tracing) – there is also mild PR depression most obviously over anterolateral leads and inferior leads plus PR elevation in aVR compared to ST segment in the same lead. This points towards concomitant acute pericarditis.

Discussion: £ The presence of LVH with LAE associated with reverse Δ sign and Spodick sign might indicate MVP associated with concomitant? acute pericarditis.

Cardiac Echo

  • Mitral valve prolapse seen with trivial MR.
  • Mild TR with mild PAH/EPAP: 39mmhg.
  • No RMWA, N Systolic and diastolic function LVEF 62%, No clot /PE, Intact septal Impression: Mitral valve prolapse with pulmonary hypertension

Dr. D. P. Khaitan, Gaya:

  • Very brilliant diagnosis.
  • Bronchiectasis in Marfan.
  • It is caused by the degeneration of fibrin fibres in the air conducting pathways +-
  • Recurrent chest infection resulting from chest deformity.
Diagnose a unique case - 17-year-old boy with wheezing, cough and haemoptysis.

CME INDIA Learning Points

  • The prevalence ranges from 1.5 to 17.2 per 100,000 individuals.
  • It is critical to make an early diagnosis of Marfan aneurysm as there is a high frequency of dissection and rupture.
  • The most life-threatening manifestations of the disorder are aortic aneurysm and dissection.
  • Now improved recognition and treatment of these outcomes have made life expectancy in Marfan syndrome nearly normal.
  • MFS (Marfan Syndrome) is an autosomal dominant, connective tissue disorder.
  • It is caused by mutations in the FIBRILLIN-1 (FBN1) gene, resulting in abnormal elastic fibers as well as increased tissue availability of transforming growth factor-beta (TGFβ).
  • Look for:
Long limbs with thin and weak wrists
Stooped shoulders
Very long and slender fingers and toes, or both
The sternum, or breastbone, protrudes or caves in
Extremely flexible joints
Long and narrow face
Small bottom jaw that may cause speech disorders
Overcrowded teeth
Slim body and taller than average height
Flat feet
High palate that may cause speech disorders
Stretch marks on the skin not due to pregnancy or weight gain
Pain in the joints, bones, and muscles
  • These are unique signs
  • The patients of Marfan syndrome may have positive thumb sign and wrist sign, also known as Steinberg sign and Walker–Murdoch sign, respectively.
  • Positive thumb sign means that the distal phalanx of the adducted thumb extends beyond the ulnar border of the palm.
  • It is elicited by asking the patient to grip his wrist with his opposite hand. If the thumb and fifth finger of the hand overlap with each other, the sign is positive.
  • Thumb and fifth finger of the hand overlap each other –Walker Murdoch sign or the wrist sign is positive.
  • Steinberg or the thumb sign is elicited by asking the patient to fold his thumb into the closed fist. If the thumb tip extends from the palm of the hand, the test is positive.
  • If the thumb tip extends from palm of hand, the test is positive – Steinberg or thumb sign is positive.
  • The thumb and wrist signs are part and parcel of the diagnostic criteria for Marfan syndrome (both Ghent 1 and Ghent 2 criteria). Therefore, both these signs aid in the diagnosis of Marfan syndrome.
  • The wrist sign indicates hypermobility and arachnodactyly, which is suggestive of Marfan syndrome, when accompanied by other signs and symptoms.
  • The wrist and thumb signs are two important signs of Marfan syndrome that aid in the diagnosis of the same. These signs can be positive in other collagen vascular diseases such as Ehler Danlos syndrome
  • The phenotype of MFS may not be apparent.
  • Its diagnosis may not be considered by clinicians.
  • The effects of MFS on the lungs and breathing are underrecognized despite the high morbidity that can occur. 
  • The phenotype is mainly characterized by cardiovascular, ocular, and skeletal manifestations.
  • The most common cardiovascular phenotype involves aortic aneurysm at the sinuses of Valsalva, which could evolve towards aortic dissection and rupture if undetected and is associated with high mortality rates.
  • Remember, the first presenting symptom of MFS patients is most commonly due to non-aortic features, including skeletal, ophthalmological, or pulmonary features
  • These respiratory effects may include chest wall and spinal deformities, emphysema, pneumothorax, sleep apnoea, and potentially increased incidence of asthma, bronchiectasis, and interstitial lung disease. 
  • Know Revised Ghent Criteria:

Diagnostic criteria for Marfan syndrome based on revised Ghent criteria

In the absence of family historyIn the presence of family history
Aortic root dilatation Z score ≥2 (when standardized to age and body size) or dissection AND ectopia lentis*Ectopia lentis AND family history of MFS
Aortic root dilatation Z score ≥2 or dissection AND FBN1 mutationA systemic score ≥7 points AND family history of MFS*
Aortic root dilatation Z score ≥2 AND systemic score ≥7 pts (when ectopia lentis is absent and the FBN1 status is either unknown or negative), an MFS diagnosis is confirmed by the presence of sufficient systemic findings (≥7 points, according to a scoring system) confirms the diagnosis*Aortic root dilatation Z score ≥2 above 20 years-old, ≥3 below 20 years-old + family history of MFS*

(Ectopia lentis AND a FBN1 mutation associated with aortic root dilatation = MFS. In the presence of ectopia lentis, but absence of aortic root dilatation/dissection, the identification of a FBN1 mutation previously associated with aortic disease is required before making the diagnosis of MFS)

  • Do you know any drug as Preventative therapy of vascular complications of MFS and implications for MFS-associated lung disease?
    • Losartan, an angiotensin II type-1 receptor (AT1R) blocker, has been implicated to prevent the aortic root dilatation of MFS in murine models and humans
    • Losartan may prevent the progression of this lung disease, albeit this is highly speculative.
    • AT1R blockade holds promise but is unproven for prevention of paraseptal emphysema and secondary pneumothorax complications.
  • 3 important differentials:

Three typical examples of HCTD (heritable connective tissue disorders

  1. Marfan syndrome (MFS),
  2. Ehlers-Danlos syndrome (EDS)
  3. Loeys-Dietz syndrome (LDS)

Tips to Pin Point


Typically characterized by cardiovascular, ocular, and skeletal manifestations.
It is caused by heterozygous mutations in FBN1, coding for the extracellular matrix (ECM) protein fibrillin-1.
The most common cardiovascular phenotype involves aortic aneurysm and dissection at the sinuses of Valsalva.



It is caused by mutations in TGBR1/2, SMAD2/3, or TGFB2/3, all coding for components of the TGFβ-signaling pathway.
LDS has unique presence of hypertelorism, bifid uvula or cleft palate, and widespread aortic and arterial aneurysm and tortuosity.
LDS cardiovascular manifestations tend to be more severe.
No association is reported between LDS and the presence of ectopia lentis, a key distinguishing feature of MFS.


Overlapping features between MFS and LDS

  • Scoliosis
  • Pes planus,
  • Anterior chest deformity
  • Spontaneous pneumothorax
  • Dural ectasia



It is group of clinically and genetically heterogeneous connective tissue disorders and all subtypes are characterized by variable abnormalities of skin, ligaments and joints, blood vessels, and internal organs.
Typical presenting features include joint hypermobility, skin hyperextensibility, and tissue fragility.
Up to one quarter of the EDS patients show aortic aneurysmal disease.
The latest EDS nosology distinguishes 13 subtypes.
Many phenotypic features show overlap between the different subtypes, which makes the clinical diagnosis rather difficult.
It highlights the importance of molecular diagnostic confirmation.

Quick Takes

Classic manifestations of MFS are cardiovascular, skeletal, and ocular Pulmonary manifestations are a bit unusual.
FBN1 gene mutation in the disease can induce a variety of effects on the respiratory system—including thoracic cage abnormalities that mechanically compromise respiratory function, airways disease (emphysema, asthma, and bronchiectasis), and sleep apne.
These induce substantial morbidity in individuals with MFS and being associated with increased mortality.

CME INDIA Tail Piece

  • Marfan syndrome MFS was first described by Antoine Bernard-Jean Marfan in 1896.
  • In 1896, in the Bulletin of the Medical Society of Paris, Antoine Marfan described a five-year-old girl with arachnodactyly.
  • It took almost 50 years to fully elucidate this syndrome including aneurysm of the ascending aorta.
  • In order to confirm the clinical impression of arachnodactyly in patients with the Marfan syndrome, Steinberg in 1966 popularized the thumb sign, which was first described by Parker and Harein 1945.
Diagnose a unique case - 17-year-old boy with wheezing, cough and haemoptysis.




3. Tun, Mon Hnin et al. “Respiratory manifestations of Marfan syndrome: a narrative review.” Journal of thoracic disease vol. 13,10 (2021): 6012-6025. doi:10.21037/jtd-21-1064

4. De Paepe A, Devereux RB, Dietz HC, Hennekam RC, Pyeritz RE. Revised diagnostic criteria for the Marfan syndrome. Am J Med Genet 1996;62:417-26.  Back to cited text no. 4   

5. Loeys BL, Dietz HC, Braverman AC, Callewaert BL, De Backer J, Devereux RB et al. The revised Ghent nosology for the Marfan syndrome. J Med Genet 2010;47:476-85.

6. Judge DP, Dietz HC. Marfan’s syndrome. Lancet. 2005:366(9501):1965-1976.

7. Reilly PR. Abraham Lincoln’s DNA and Other Adventures in Genetics. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press; 2000.

Discover CME INDIA:

Discover CME INDIA