Hunter syndrome (Mucopolysaccharidosis II)

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.

Hunter syndrome (mucopolysaccharidosis II) is an X-linked lysosomal storage disorder caused by abnormal accumulation of glycosaminoglycans in tissues throughout the body. It occurs predominantly in males, although females can rarely be affected. A distinctive presentation may include characteristic coarse facies, clear corneas, growth deficiency, and stiff joints.

It can present with psychiatric features such as hyperactivity, impulsivity, aggression, anxiety, behavioural difficulties, and sleep disturbance. Autism spectrum disorder (ASD) has also been described, particularly in children with the neuronopathic form. These neurobehavioural manifestations are predominantly childhood-onset and may evolve alongside progressive cognitive deterioration; late-onset new psychiatric presentations in adulthood are not typical.

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

  • Macrocephaly

  • Coarse face

  • Thick vermilion

  • Large tongue

  • Alveolar ridge overgrowth

Other characteristic features include developmental delay and progressive cognitive impairment in the neuronopathic form, seizures, hydrocephalus, and progressive neurological deterioration. Other important manifestations include hepatosplenomegaly, short stature, dysostosis multiplex, carpal tunnel syndrome, hearing loss, and progressive airway and cardiac disease.

Early diagnosis is important to identify progressive neurological, respiratory, cardiac, skeletal, and other systemic complications; to distinguish neuronopathic from non-neuronopathic disease; and to allow early multidisciplinary management and consideration of available disease-specific treatment and supportive interventions.

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.