Fragile X syndrome (FXS, Martin-Bell syndrome, Marker X syndrome)

Page most recently updated 7 September 2026

This page focuses on the reported psychiatric associations, which may be the initial presenting manifestation, and on other clinical features that may assist the psychiatrist or primary care physician in identifying the underlying diagnosis, considered through the lenses of the diagnostic lenses framework.

Fragile X syndrome is a genetic disorder that can affect neurodevelopment, mental health, and multiple organ systems. It can occur as an inherited genetic condition; de novo full-mutation cases are uncommon. It predominantly affects males, who are generally more substantially affected than females. Fragile X can show a pattern of increasing numbers of affected individuals across successive generations, as an FMR1 premutation may expand to a full mutation when transmitted from a mother. Thus, psychiatric, developmental, or intellectual difficulties in multiple members of successive generations may be an important clue to the diagnosis; family history should therefore explore unexplained developmental, intellectual, psychiatric, or behavioural difficulties in earlier generations, rather than asking only for a family history of formally diagnosed Fragile X syndrome.

Distinctive features may include the combination of intellectual disability, macroorchidism, and connective-tissue features such as lax or hypermobile joints, soft or hyperextensible skin, flat feet, and related skeletal findings.

It can present with psychiatric features such as anxiety, attention-deficit symptoms, autism-spectrum features, social difficulties, mood instability, irritability, aggression, obsessive-compulsive symptoms, and, rarely, psychosis. Psychiatric manifestations may become apparent or clinically significant during adolescence or adulthood.

From a morphologic lens perspective, other features include (but are not limited to):

  • Prognathism

  • Epicanthus

  • Broad nasal bridge

Other characteristic features include developmental delay, intellectual disability of variable severity, speech and language difficulties, learning difficulties, hypotonia, motor-coordination difficulties, autism-spectrum disorder, and seizures in some individuals. Macrocephaly, a long face, prominent forehead, and prominent ears are characteristic craniofacial features that may become more apparent with age.

From a multisystemic lens perspective, clinical features in other body systems include (but are not limited to):

  • Cardiovascular: mitral valve prolapse and aortic root dilatation may occur, particularly in adulthood.

  • Respiratory: recurrent respiratory infections and sleep-disordered breathing may occur.

  • Gastrointestinal: gastroesophageal reflux and other gastrointestinal or feeding difficulties may occur.

  • Endocrine: obesity may occur.

  • Musculoskeletal: joint laxity or hypermobility, pes planus, scoliosis, and other connective-tissue-related skeletal abnormalities may occur.

  • Dermatologic: soft or hyperextensible skin and other mild connective-tissue abnormalities may occur.

Early diagnosis is important to identify potentially treatable medical contributors to psychiatric, developmental, and cognitive presentations, recognize associated cardiovascular, neurologic, gastrointestinal, musculoskeletal, and other systemic complications, guide appropriate developmental and educational support and medical surveillance, and enable timely treatment of psychiatric illness and other comorbidities.

Selected references and further reading — Morphologic lens

Jones KL, Jones MC, del Campo M. Smith's recognizable patterns of human malformation. 8th ed. Philadelphia: Elsevier; 2021.

Reardon W. The bedside dysmorphologist: a guide to identifying and assessing congenital malformations. 2nd ed. Oxford: Oxford University Press; 2016.

Allanson JE, Biesecker LG, Carey JC, Hennekam RCM. Elements of morphology: introduction. Am J Med Genet A. 2009;149A(1):2-5. doi:10.1002/ajmg.a.32601.

Hennekam RCM, Biesecker LG, Allanson JE, Hall JG, Opitz JM, Temple IK, Carey JC; Elements of Morphology Consortium. Elements of morphology: general terms for congenital anomalies. Am J Med Genet A. 2013;161A(11):2726-2733. doi:10.1002/ajmg.a.36249.

Selected references and further reading — Multisystemic lens

Cardinal RN, Bullmore ET. The diagnosis of psychosis. Cambridge: Cambridge University Press; 2011.

Sachdev PS, Keshavan MS, editors. Secondary schizophrenia. Cambridge: Cambridge University Press; 2010.

Levenson JL, editor. The American Psychiatric Association Publishing textbook of psychosomatic medicine and consultation-liaison psychiatry. 3rd ed. Washington (DC): American Psychiatric Association Publishing; 2019.

Stern TA, Beach SR, Smith FA, Freudenreich O, Vranceau AM, Fava M, editors. Massachusetts General Hospital handbook of general hospital psychiatry. 8th ed. Philadelphia: Elsevier; 2025.

Arciniegas DB, Yudofsky SC, Hales RE, editors. The American Psychiatric Association Publishing textbook of neuropsychiatry and clinical neurosciences. 6th ed. Washington (DC): American Psychiatric Association Publishing; 2018.

Agrawal N, Faruqui R, Bodani M, editors. Oxford textbook of neuropsychiatry. Oxford: Oxford University Press; 2020.

Boland R, Verduin M, editors. Kaplan and Sadock's comprehensive textbook of psychiatry. 11th ed. Philadelphia: Wolters Kluwer; 2024.

Loscalzo J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, editors. Harrison's principles of internal medicine. 22nd ed. New York: McGraw Hill; 2025.