Pectus carinatum in Marfan syndrome

Disclosure: M.C. Duarte: None. R. Mattos: None. T.R. Costa: None. I.S. Freitas: None. J.B. Drummond: None. B.S. Soares: None.Introduction: Marfan Syndrome (MFS) is an autosomal hereditary disorder with skeletal, ocular, and cardiovascular manifestations, while acromegaly results from excess growth hormone (GH), leading to skin thickening, extremity enlargement, and macroglossia. Both conditions are individually described, but their coexistence is rare. This case presents a unique instance of both MFS and acromegaly in one patient.Case: A 56-year-old male with classic features of MFS, including joint laxity, pectus carinatum, arm span-to-height ratio of 1.06, and positive thumb and wrist signs, also had significant cardiovascular involvement, having undergone aortic valve replacement and aneurysmectomy of the descending aorta. Despite a negative family history, his clinical features met MFS diagnostic criteria. Ten years after diagnosis, he noticed progressive changes in his hands, feet, and facial features, including a prominent nose, lips, and jaw.He sought endocrinological evaluation, and during the physical examination, signs of joint swelling and severe heart failure symptoms, including dyspnea, bilateral leg edema, and a grade V systolic murmur, were noted.Laboratory tests showed elevated IGF-1 (346 ng/mL) and GH (11 ng/mL) levels after an oral glucose tolerance test. MRI revealed a macroadenoma (1.2x0.8x0.8 cm). Due to his decompensated heart condition, surgery was postponed, and he began monthly lanreotide injections (120 mg), which reduced IGF-1 to 256 ng/mL and improved symptoms of aortic insufficiency and heart failure. One year later, cabergoline (1.5 mg/week) was added, and MRI showed tumor shrinkage (1.0x0.8x0.7 cm), though IGF-1 remained elevated at 296 ng/mL. After stabilizing his cardiac condition, the patient underwent transsphenoidal surgery. One month post-surgery, IGF-1 levels normalized, and he reported relief from swelling and pain.Whole exome sequencing (NGS) revealed no pathogenic variants linked to MFS, Multiple Endocrine Neoplasia type 1 and/or Isolated Familial Acromegaly. However, several potential pathogenic variants were identified in heterozygous form across six genes: WDR87 (p.Arg131Ter), POLR3A (c.1909+22G>A), CTNS (48 kb deletion), DUOX (p.Ser205Ter), FLG (p.Arg501Ter), and HFE (p.Cys282Tyr), though their clinical relevance is uncertain.Discussion:. In patients with Marfan-like phenotypes, fewer than 10% show pathogenic variants in the FBN1 gene, possibly due to complex genetic alterations. The identification of potential pathogenic variants in multiple genes highlights the complexity of genetic contributions to the patient’s condition, warranting further investigation. The coexistence of MFS and acromegaly in a single patient raises significant considerations about the diagnostic process, treatment strategies, and genetic evaluation for complex diseases.Presentation: Monday, July 14, 2025

Marfan Syndrome (MFS) is a systemic disorder caused by mutations in fibrillin-1. The most common cause of mortality in MFS is dissection and rupture of the aorta. Due to a highly variable and age-dependent clinical spectrum, the diagnosis of MFS still remains sophisticated. The aim of the study was to determine if there exist phenotypic features that can play the role of “red flags” in cases of MFS suspicion. The study population included 306 patients (199 children and 107 adults) who were referred to the Department of Pediatric Cardiology due to suspicion of MFS. All patients underwent complete clinical evaluation in order to confirm the diagnosis of MFS according to the modified Ghent criteria. MFS was diagnosed in 109 patients and marfanoid habitus in 168 patients. The study excluded 29 patients with other hereditary thoracic aneurysm syndromes. Comparative analysis between patients with Marfan syndrome and marfanoid habitus was performed. Symptoms with high prevalence and high positive likelihood ratio were identified (pectus carinatum, reduced elbow extension, hindfoot deformity, gothic palate, downslanting palpebral fissures, lens subluxation, myopia ≥ 3 dioptres remarkably high stature). The differentiation between patients with MFS and marfanoid body habitus is not possible by only assessing external body features; however, “red flags” could be helpful in the screening phase.

Manifestations respiratoires du syndrome de Marfan

Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder resulting from dysregulation of transforming growth factor Β (TGFB) signaling. LDS results from pathogenic variants in several genes including TGFBR1, TGFBR2, SMAD2, SMAD3, TGFB2, and TGFB3, and PMEPA1 with variable manifestations and several subtypes. LDS shares phenotypic resemblance with Marfan syndrome, with the most important consequence being a predisposition to aneurysm and dissection of arteries throughout the body, especially the aortic root. Other clinical manifestations include chest wall anomalies (pectus excavatum and pectus carinatum) (33-51%), scoliosis (27-85%), food and environmental allergic sensitization (31-50%), hypertelorism, bifid uvula/cleft palate (9-37%), malar hypoplasia (60-100%), micro/retrognathia (10-50%), clubfoot, thin translucent skin, and connective tissue issues such as joint laxity and hernia. The prevalence of pulmonary manifestations of LDS is largely unknown, though some extrapolation from Marfan syndrome has been made. Chest wall and spinal anomalies may lead to restrictive or obstructive changes in lung function. Allergic sensitization may be associated with asthma. Craniofacial anomalies may predispose to obstructive sleep apnea syndrome. Connective tissue weakness may predispose to pneumothorax, bronchiectasis, emphysema, or altered gas exchange. We reviewed pulmonary function test (PFT) data from the National Institutes of Health LDS cohort to assess the prevalence of PFT abnormalities in this disorder. The cohort included 80 subjects seen in the NIH Clinical Center who underwent pulmonary function testing during their visit. Testing included spirometry, plethysmography or multibreath nitrogen washout, DLCO, MIP, MEP, and fraction of exhaled nitric oxide (FENO). Mean age of the cohort was 30 years with a range of 6-71 years. 33% of the cohort was male and 67% female. Results show 37.5% manifested an obstructive defect, 14% a restrictive defect, and 23.5% abnormal diffusion. Evidence of asthma or eosinophilic inflammation was common with a positive bronchodilator response in 17.5% and elevated FENO in 34.8%. 42% had inspiratory and/or expiratory muscle weakness. Our conclusion is that pulmonary manifestations are common but varied in LDS. Most subjects had mild anomalies. It is likely that chest wall and spine anomalies contribute to the majority of obstructive and restrictive deficits while allergic sensitization to the bronchodilator response and elevated FENO. Future work will focus on characterizing pulmonary function manifestations with respect to phenotypic manifestations and underlying genetic cause /LDS subtype, as well as the nature of gas exchange and respiratory muscle abnormalities.

Marfan Syndrome is a rare connective tissue condition that affects several systems, including musculoskeletal, cardiovascular and ocular systems. Although less frequent, pulmonary involvement can nevertheless lead to emphysema, bullae, apical blebs, and a higher risk of spontaneous pneumothorax. Another option is pectus excavatum, carinatum, or scoliosis-related restrictive lung disease. We will discuss a case of 18 year old girl, with marfanoid habitus, non-smoker with history of ATT taken on radiological grounds, with complains of shortness of breath on and off and presenting with sudden onset worsening of shortness of breath and dry cough for 3 weeks. Chest x-ray showed tension pneumothorax. After emergency management echo was done and it showed MVP with MR. Patient was diagnosed as a case of Marfan Syndrome following Ghent criteria. The case indicates that pneumothorax though rare can be first presentation of Marfan Syndrome.

Marfan syndrome is caused by mutations in the fibrillin-1 gene (FBN1). The most important features affect the cardiovascular system, eyes, and skeleton. The aim of this study was to report the most frequent musculoskeletal alterations observed in 146 patients affected by Marfan syndrome. Fifty-four patients (37%) underwent cardiac surgery and 11 of them received emergent surgery for acute aortic dissection. Ectopia lentis was found in 68 patients (47%) whereas myopia above 3D occurred in 46 patients (32%). Musculoskeletal anomalies were observed in all patients with Marfan syndrome. In 88 patients (60.2%), the associated “wrist and thumb sign” was present; in 58 patients (39.7%), pectus carinatum deformity; in 44 patients (30.1%), pectus excavatum; in 49 patients (33.5%), severe flatfoot; in 31 patients (21.2%), hindfoot deformity; in 54 patients (36.9%), reduced US/LS ratio or increased arm span-height ratio; in 37 patients (25.3%), scoliosis or thoracolumbar kyphosis; in 22 patients (15%), reduced elbow extension (170° or less). Acetabular protrusion was ascertained on radiographs in 27 patients (18.4%). Orthopaedic aspects of the disease are very important for an early diagnosis; however, we have not observed definite correlations between the extent of orthopaedic involvement and aortic complications.

Marfan Syndrome, an autosomal dominant, generalized disorder affecting the connective tissue, caused by mutations of FBN 1 gene which leads to deficiency of fibrillin 1 leading to reduced microfibril formation and disrupts the mechanical integrity of connective tissue, presents a complex clinical picture affecting multiple systems, poses significant challenges to conventional management. We present an 18-year-old female with Marfan Syndrome, highlighting her clinical features such as thin and slender body with disproportionately long arms and legs as compared with the trunk, bilateral Ectopia lentis, Arachnodactyly, positive Walker Murdoch Wrist sign and positive Steinberg Thumb sign, bilateral Pes planus, asymmetrical chest with mild Pectus carinatum deformity and moderate degree of Kyphoscoliosis along with winging of scapula. This article explores the Ayurvedic concept of Beeja dosha and highlights the value of integrating Ayurvedic insights into the management of Marfan Syndrome, offering a holistic and personalized approach to patient care to improve the quality of life and aims to deepen understanding of Marfan Syndrome from an Ayurvedic perspective, laying the groundwork for future research into Ayurvedic management strategies.