Endocrine Abstracts

JOINT3535

Introduction: Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the FBN1 gene, typically affecting the cardiovascular, skeletal, and ocular systems. While diagnosis is usually made clinically, genetic testing is often required in atypical cases to confirm the diagnosis. This report presents a 12-year-old girl diagnosed with Marfan syndrome through genetic testing despite lacking classic cardiovascular and ocular symptoms typically associated with the condition.

Case report: The patient was referred for evaluation due to accelerated growth to the endocrinologist. She also reported fatigue, shortness of breath on exertion, and frequent urination. The patient was born from a first pregnancy. She had a sibling who passed away the day after birth, the father does not recall the cause of death. This family history raises the possibility of a hereditary condition. On examination, she had a tall, thin body, long fingers (arachnodactyly), and pectus carinatum, scoliosis, pectus carinatum, joint hypermobility, and stretch marks. However, she did not exhibit cardiovascular or ocular symptoms, such as aortic dilation or lens dislocation, which are classically associated with Marfan syndrome. Echocardiography: normal heart function with no evidence of aortic root dilation, though an incidental mitral annular ring was noted. Her ophthalmologic examination was normal. Genetic testing identified a heterozygous pathogenic variant in the FBN1 gene (c.4930C>T, p.Arg1644Ter), confirming Marfan syndrome. This nonsense mutation results in a truncated fibrillin-1 protein, which plays a crucial role in connective tissue integrity. The variant is classified as pathogenic (ClinVar ID: VCV000200186), with a likely de novo inheritance, though parental testing is recommended.

Discussion: This case highlights the variability in Marfan syndrome presentation, particularly in patients without significant cardiovascular or ocular involvement. Despite the absence of aortic dilation or lens dislocation, skeletal features such as scoliosis and pectus carinatum were consistent with the diagnosis. Genetic confirmation of the FBN1 mutation was essential, as clinical criteria alone may not have been sufficient for diagnosis. Although the patient does not currently exhibit life-threatening cardiovascular complications, regular monitoring is crucial, as these issues may develop over time. Marfan syndrome is a progressive condition, and aortic dilation, mitral valve prolapse, and lens dislocation can emerge later in life.

Conclusion: Although the patient currently lacks cardiovascular and ocular abnormalities, ongoing surveillance and multidisciplinary care are essential to managing long-term risks. Regular cardiovascular, ophthalmologic, and orthopedic monitoring, along with genetic counseling, will be key in ensuring early detection and intervention for potential complications.