Gender and psychiatric manifestations in Marfan syndrome – is there a link?

To the Editor

We report a case of Marfan syndrome (MFS) co-morbid with schizophrenia. A 20-year-old lady presented with a history of thought broadcast, thought insertion, thought withdrawal, third person auditory hallucinations and delusions of reference and persecution. A diagnosis of paranoid schizophrenia was made. As the patient was unusually tall, had long slender fingers and a high arched palate, a detailed evaluation for MFS was conducted and was found to satisfy revised Ghent criteria for the same. Cardiology evaluation revealed mitral valve prolapse and the patient was asked to return for regular follow-up. Her psychotic symptoms improved with olanzapine. A detailed family history revealed that two of the patient’s paternal aunts who had features suggestive of marfanoid habitus suffered from severe depression and both of them committed suicide. Two of her father’s maternal aunts who had history suggestive of psychosis also had marfanoid habitus. The patient’s father and his two brothers who had marfanoid habitus did not have any diagnosable psychiatric condition. In addition two of her paternal aunts who did not have marfanoid habitus were also asymptomatic.

MFS is a variable autosomal dominant disorder characterized by connective tissue defects in multiple organ systems aetiologically linked to a mutation in the fibrillin 1 gene on chromosome 15. This syndrome has been associated with schizophrenia and common pathophysiological mechanisms that have been proposed include aberrant transforming growth factor beta (TGF-β) signalling in both disorders (Bossche et al., 2012). TGF-β has been implicated in tall as well as short stature (Goff and Daire, 2012). Evidence suggests that females with psychosis may have altered skeletal growth trajectory (Welham et al., 2009). Although many case reports from the available literature on MFS and psychiatric problems don’t specify the gender of the patient, the few reports that do have been largely in females (Bossche et al., 2012). An interesting finding from the exploration of family history in this case was the presence of psychiatric morbidity predominantly in female relatives with marfanoid habitus.

Hence females with MFS or marfanoid habitus may be at a higher risk of developing psychiatric problems. Evidence for this is suggestive at best and further research is required.