Voice Symptoms and Quality of Life in Individuals With Marfan Syndrome: A Cross-Sectional Study



      Marfan Syndrome (MFS) is a connective tissue disorder that affects skeletal, ocular, pulmonary, cardiovascular, and central nervous systems. Symptoms may lead to diminished quality of life (QoL) in individuals with MFS compared with healthy individuals. Currently, there is little evidence regarding the impact of MFS on voicing and QoL. This study examined perceptions of voicing difficulties and QoL among persons with MFS.


      A total of 356 participants with a self-reported diagnosis of MFS completed the Quality-of-Life Index (QLI) and voice handicap index–10 (VHI-10) and provided medication regime.


      Some degree of voice handicap was reported by a majority of participants. Analyses assessing correlations between responses to the VHI-10, QLI scores, and reported medications were conducted. Specific medications and responses on the VHI-10 were significantly associated with QLI scores. Multiple regression analyses revealed that a summed VHI-10 score was the strongest predictor of QLI satisfaction, QLI importance, and overall QLI.


      The findings of the current study suggest that individuals with MFS may experience self-perceived phonatory dysfunction which impact QoL. Specific classes of drugs may also be associated with reported voice handicap and QoL satisfaction in MFS. These findings have implications for physicians and clinicians who work with individuals with MFS.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Voice
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Callewaert B
        • Malfait F
        • Loeys B
        • et al.
        Ehlers-Danlos syndromes and Marfan syndrome.
        Best Pract Res Clin Rheumatol. 2008; 22: 165-189
        • Goldfinger JZ
        • Preiss LR
        • Devereux RB
        • et al.
        Eagle KA for the GenTAC Registry Consortium. Marfan syndrome and quality of life in the GenTAC registry.
        J Am Coll Cardiol. 2017; 69: 2821-2830
        • Nelson AM
        • Walega DR
        • McCarthy RJ
        The incidence and severity of physical pain symptoms in Marfan syndrome: a survey of 993 patients.
        Clin J Pain. 2015; 31: 1080-1086
        • Rand-Hendriksen S
        • Sørensen I
        • Holmström H
        • et al.
        Fatigue, cognitive functioning and psychological distress in Marfan syndrome, a pilot study.
        Psychol Health Med. 2007; 12: 305-313
        • Behr CA
        • Denning N
        • Kallis MP
        • et al.
        The incidence of Marfan syndrome and cardiac anomalies in patients presenting with pectus deformities.
        J Pediatr Surg. 2019; 54: 1926-1928
        • Fusar-Poli P
        • Klersy C
        • Stramesi F
        • et al.
        Determinants of quality of life in Marfan syndrome.
        Psychosomatics. 2008; 49 (Available at:): 243-248
        • Milewicz DM
        • Dietz HC
        • Miller C
        Treatment of aortic disease in patients with Marfan syndrome.
        Circulation. 2005; 111: e150-e157
        • Matkar PN
        • Chen HH
        • Leong-Poi H
        • et al.
        Overview of Marfan syndrome: knowns and unknowns.
        J Controversies Biomed Res. 2015; 1: 51-66
        • Aubart M
        • Gross M
        • Hanna N
        • et al.
        The clinical presentation of Marfan syndrome is modulated by expression of wild-type FBN1 allele.
        HumMol Genet. 2015; 24: 2764-2770
        • Du Q
        • Zhang D
        • Zhuang Y
        • et al.
        The molecular genetics of Marfan syndrome.
        Int J Med Sci. 2021; 18: 2752-2766
        • Groth KA
        • Hove H
        • Kyhl K
        • et al.
        Prevalence, incidence, and age at diagnosis in Marfan syndrome.
        Orphanet J Rare Dis. 2015; 10: 1-10
        • Meester JAN
        • Verstraeten A
        • Schepers D
        • et al.
        Differences in manifestations of Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome.
        Ann Cardiothorac Surg. 2017; 6: 582-594
        • Otremski H
        • Widmann RF
        • Di Maio MF
        • et al.
        The correlation between spinal and chest wall deformities and pulmonary function in Marfan syndrome.
        J Child Orthop. 2020; 14: 343-348
        • Singh AA
        • Velineni R
        • Varty K
        • et al.
        Bilateral extracranial internal carotid artery aneurysms in a patient with Marfan syndrome: case report and review of the literature.
        EJVES Short Rep. 2019; 45: 14-16
        • Schwartz SR
        • Cohen SM
        • Dailey SH
        • et al.
        Clinical practice guideline: hoarseness (dysphonia).
        Otolaryngol Head Neck Surg. 2009; 141: S1-S31
        • Spadafora P
        • Esposito A
        • Giannitto C
        • et al.
        Vascular causes of dysphonia: a case series with different etiologies.
        Rep Med Imaging. 2021; 14: 65-70
        • Stachler RJ
        • Francis DO
        • Schwartz SR
        • et al.
        Clinical practice guideline: Hoarseness (dysphonia) (update).
        Otolaryngology-Head Neck Surg. 2018; : 1-42
        • Teixido MT
        • Leonett JP
        Recurrent laryngeal nerve paralysis associated with thoracic aortic aneurysm.
        Otolaryngol Head Neck Surg. 1990; 102: 140-144
        • Dutra BL
        • Campos LC
        • Marques HC
        • et al.
        Ortner's syndrome: a case report and literature review.
        Radiologia Brasileira. 2015; 48: 260-262
        • Vahabzadeh-Hagh AM
        • Zhang Z
        • Chhetri DK
        Hirano's cover-body model and its unique laryngeal postures revisited.
        Laryngoscope. 2018; 128: 1412-1418
        • Aronson AE
        • Bless DM
        Clinical Voice Disorders.
        4th ed. Thieme Medical Publishers, Inc., New York, NY2009
        • Chohan K
        • Mittal N
        • McGillis L
        • et al.
        A review of respiratory manifestations and their management in Ehlers-Danlos syndromes and hypermobility spectrum disorders.
        Chronic Respir Dis. 2021; 18: 1-14
        • Jeffery T
        • Postavaru GI
        • Matei R
        • et al.
        I have had to stop singing because I can't take the pain’: experiences of voice, ability, and loss in singers with hypermobility spectrum disorders.
        J Voice. 2021;
        • Iacovou E
        • Vlastarakos PV
        • Nikolopoulos TP
        Laryngeal involvement in connective tissue disorders. Is it important for patient management?.
        Indian J Otolaryngol Head Neck Surg. 2014; 66: S22-S29
        • Tateya T
        • Tateya I
        • Bless DM
        Collagen subtypes in human vocal folds.
        Ann Otol Rhinol Laryngol. 2006; 115: 469-476
        • Roy N
        • Bless DM
        Personality traits and psychological factors in voice pathology: a foundation for future research.
        J Speech, Lang Hear Res. 2000; 43: 737-748
        • Bowen JM
        • Connolly HM
        Of Marfan's syndrome, mice, and medications – editorial.
        New Engl JMed. 2014; 371: 2127-2128
        • Jobski K
        • Hoffman F
        • Herget-Rosenthal S
        • et al.
        Drug interactions with oral anticoagulants in German nursing home residents: comparison between vitamin K antagonists and non-vitamin K antagonist oral anticoagulants based on two nested case-control studies.
        Clin Res Cardiol. 2020; 109: 465-475
        • Osawa H
        • Kita H
        • Ohnishi H
        • et al.
        Histamine-2 receptor expression in gastric mucosa before and after Helicobacter pylori cure.
        Aliment Pharmacol Ther. 2005; 21: 92-98
        • Wallace JL
        • Soldato PD
        The therapeutic potential of NO-NSAIDs.
        FundamClin Pharmacol. 2002; 17: 11-20
        • Boer CG
        • Szilagyi I
        • Nguyen NL
        • et al.
        Vitamin K antagonist anticoagulant usage is associated with increased incidence and progression of osteoarthritis.
        Ann Rheum Dis. 2021; 80: 598-604
        • Paulsen FP
        • Tillmann BN
        Osteoarthritis in cricoarytenoid joint.
        Osteoarthritis Cartilage. 1999; 7: 505-514
      1. Nemr K, Di Carlos Silva A, Rodrigues DA, et al. Medications and adverse voice effects. J Voice. 2017;32:515.e29-515.e39.

        • Harris TM
        • Kariyawasam HH
        • Rubin JS
        The voice and medications.
        (eds)in: Rubin JS Sataloff RT Korovin GS Diagnosis and Treatment of Voice Disorders. 4th ed. Plural Publishing, Inc., San Diego, CA2014: 617-629
        • Finger ME
        • Madden LL
        • Haq IU
        • et al.
        Analysis of the prevalence and onset of dysphonia and dysphagia symptoms in movement disorders at an academic medical center.
        J Clin Neurosci. 2019; 64: 111-115
        • Rosen CA
        • Lee AS
        • Osborne J
        • et al.
        Development and validation of the voice handicap index-10.
        Laryngoscope. 2004; 114: 1549-1556
        • Ferrans CE
        • Powers MJ
        Quality of life index: development and psychometric properties.
        Adv Nurs Sci. 1985; 8: 15-24
        • Arffa RE
        • Krishna P
        • Gartner-Schmidt J
        • et al.
        Normative values for the Voice Handicap Index-10.
        J Voice. 2012; 26: 462-465
        • Benninger MS
        • Holy CE
        • Bryson PC
        • et al.
        Prevalence and occupation of patients presenting with dysphonia in the United States.
        J Voice. 2017; 31: 594-600
        • Hunter A
        • Morgan AW
        • Bird HA
        A survey of Ehlers-Danlos syndrome: hearing, voice, speech and swallowing difficulties. Is there an underlying relationship?.
        Rheumatology. 1998; 37: 803-804
        • Rimmer J
        • Giddings CEB
        • Cavalli L
        • et al.
        Dysphonia – A rare early symptom of Ehlers-Danlos syndrome?.
        Int J Pediatr Otorhinolaryngol. 2008; 72: 1889-1892
        • Sasaki CT
        • Young N
        • Matsuzaki H
        • et al.
        Anatomy of the human larynx.
        (eds)in: Rubin JS Sataloff RT Korovin GS Diagnosis and Treatment of Voice Disorders. 4th ed. Plural Publishing, Inc., San Diego, CA2014: 44-45
        • Zemlin WR
        Speech and Hearing Science: Anatomy and Physiology.
        4th ed. Allyn and Bacon, Boston, MA1998
        • Colton RH
        • Casper JK
        • Leonard R
        Understanding Voice Problems: A Physiological Perspective for Diagnosis and Treatment.
        4th ed. Lippincott Williams & Wilkins, Philadelphia, PA2011
        • Tang SS
        • Mohad V
        • Gowda M
        • et al.
        Insights into the role of collagen in vocal fold health and disease.
        J Voice. 2017; 31: 520-527
        • Trajano FMP
        • Almeida LNA
        • Leite de Alencar SA
        • et al.
        Group voice therapy reduces anxiety in patients with dysphonia.
        J Voice. 2019; 34: 702-708
        • Mirza N
        • Ruiz C
        • Baum ED
        • et al.
        The prevalence of major psychiatric pathologies in patients with voice disorders. ENT-Ear.
        Nose Throat J. 2003; : 808-814
        • Liu CY
        • Yu JM
        • Wang NM
        • et al.
        Emotional symptoms are secondary to the voice disorder in patients with spasmodic dysphonia.
        Gen Hosp Psychiatry. 1998; 20: 255-259
        • Watts CH
        • Vanryckeghem M
        Communication-related affective, behavioral, and cognitive reactions in speakers with spasmodic dysphonia.
        Laryngoscope Investig Otolaryngol. 2017; 2: 466-470
        • Ratiu I
        • Virden TB
        • Baylow H
        • et al.
        Executive function and quality of life in individuals with Marfan syndrome.
        Qual Life Res. 2018; 27: 2057-2065
        • Vanem TT
        • RandHendriksen S
        • Brunborg C
        • et al.
        Health- related quality of life in Marfan syndrome: a 10-year follow-up.
        Health Qual Life Outcomes. 2020; 18: 1-8
        • Afkhami M
        • Amirishavaki Y
        • Qhelichi L
        Correlation between vocal fatigue index and voice handicap index scores in persons with laryngeal pathologies.
        Funct Disabil J. 2019; 2: 119-124
        • Peters KF
        • Apse KA
        • Blackford A
        • et al.
        Social and behavioral research in clinical genetics. Living with Marfan syndrome: coping with stigma.
        Clin Genet. 2005; 68: 6-14
        • Lee VC
        • Rhew DC
        • Dylan M
        • et al.
        Meta-analysis: angiotensin-receptor blockers in chronic heart failure and high-risk acute myocardial infarction.
        Ann Internal Med. 2004; 141: 693-704
        • Brody DJ
        • Gu Q
        Antidepressant use among adults: United States. 2015-2018.
        NCHS Data Brief. 2020; (no 377): 1-8
        • Young VVN
        Patients’ attitudes regarding treatment for vocal fold atrophy.
        J Voice. 2019; 34: 763-768