LAUSR

Although an association between Marfan syndrome and schizophrenia has long been queried, the available supportive evidence is largely anecdotal [1], and their cooccurrence in individual cases may thus be coincidental [8]. Moreover, most of the published case reports have not included confirmatory fibrillin-1 (FBN1) gene testing, and rather have relied on clinical features to make the diagnosis of Marfan syndrome. As such, in at least some cases, the observed phenotypes may have occurred secondary to other similarly presenting genetic disorders that better account for the comorbid development of psychosis. Despite the historic interest in this topic, up-to-date diagnostic considerations for psychiatrists when psychotic symptoms are encountered on the background of a Marfan-like phenotype are scarcely described in the literature. As such, a succinct review of this focused topic is presented here. The two genetic disorders that most clearly predispose to the development of psychotic symptoms in combination with a Marfanoid habitus, are Lujan–Fryns syndrome and cystathionine beta synthase (CBS) deficiency. Lujan–Fryns syndrome, which results from variants in the MED12 gene on the X chromosome [3], is characterized by mild-to-moderate intellectual disability in association with numerous suggestive craniofacial features, that most notably include a prominent forehead with a long narrow face and maxillary hypoplasia, in addition to tall stature, long and thin digits, hyper-extensible joints, hypotonia, hypernasal speech, and pectus excavatum [7]. Variable psychiatric symptoms also occur in the majority of patients, with autistic features being the most common; however, schizophrenia-like presentations have also frequently been described, albeit in only a minority of individuals [3]. CBS deficiency is an inborn error of homocysteine metabolism (due to variants in the CBS gene at 21q22.3) that results in homocystinuria, and that is characterized by lens dislocations, myopia, osteoporosis, and thromboembolic events, in addition to tall stature, long narrow limbs, scoliosis, and pectus excavatum, notably without joint hypermobility [5]. A variety of non-specific psychiatric symptoms, including psychosis, also frequently occur and may rarely be the presenting feature [2, 4]. One other rare and more recently described disorder that should also be considered in this context is 3q27.3 microdeletion syndrome, which is associated with developmental delay, variable intellectual disability, and numerous dysmorphic features, including a hooked nose and high nasal bridge, deep-set eyes, a short philtrum, thin upper lip, small mouth, low-set ears, prognathism, and a slender face, in addition to a long, thin body habitus, scoliosis, and arachnodactyly [6]. Psychiatric symptoms, including psychosis (particularly in association with mood disorders), have also been described in numerous individuals [6]. While not classically Marfanoid in appearance, additional conditions that are commonly excluded prior to pursuing a diagnostic workup for the aforementioned disorders, include Klinefelter syndrome and Fragile-X syndrome. In the absence of severe neurodevelopmental abnormalities or unexplained cooccurring medical issues, individuals with a schizophrenia spectrum illness are unlikely to initially come to the attention of medical specialists outside of psychiatry. As such, when Marfanoid features, which may be quite striking even to clinicians untrained in dysmorphology, are observed in patients with a history of psychosis, genetic testing should be strongly considered by the attending psychiatrist. At a minimum, testing should include a plasma or serum homocysteine level to screen * Mark Ainsley Colijn [email protected]