Early 'red flag' signs and symptoms

The presentation and course of symptoms varies amongst Hunter syndrome patients. However, early non-neuronopathic symptoms that could raise the suspicion of Hunter syndrome include:1,2

  • otitis media
  • abdominal hernia
  • nasal obstruction
  • enlarged liver/spleen
  • enlarged tonsil/adenoids and tongue
  • large head circumference

However, these are non-specific and relatively common occurrences in childhood. This can disguise the underlying Hunter syndrome pathology, hindering early identification and management.2 Similarly, neuronopathic symptoms such as hyperactivity, obstinacy and aggression can overlap with normal childhood behaviours.3 The crucial distinction between common childhood problems and Hunter syndrome is the occurrence of non-neuronopathic symptoms repeatedly, and in clusters.

When early symptoms are overlooked, the delay between symptom presentation and diagnosis can be substantial. In such cases, initial suspicion of Hunter syndrome arises due to more advanced features of the disease, such as the observation of facial dysmorphism.

The important point is if they’re occurring in combination, if they’re occurring earlier in life than you’d usually expect, and if they’re particularly severe or refractory to treat. Then you should think about the possibility of these unrelated conditions as an underlying diagnosis

- Dr David Whiteman

Learn more about how Hunter syndrome is diagnosed

Multisystemic involvement

Click on an organ system to view the clusters of symptoms that should raise the suspicion of Hunter syndrome.


    • Developmental delay (e.g. speech, walking)3
    • Progressive cognitive debilitation3
    • Behavioural issues (e.g. hyperactivity, obstinacy and aggression)3
    • Normal at birth, with large head circumference2
    • Facial features from ages 2–4 years: broad nose with flared nostrils, prominent brow, large jowls and thick lips2
    • Loss of visual acuity or vision (due to elevated intraocular pressure, retinal pigmentary degeneration, optic disc swelling* (papilloedema), scleral thickening*, and optic atrophy*)2

    * Resulting from neuronopathic causes

    • Umbilical and inguinal hernias2
    • Distended abdomen (due to an enlarged liver and spleen)2
    • Bladder obstruction2
    • Chronic diarrhoea*2

    * Resulting from neuronopathic causes


    Valve disease leading to left and right ventricle hypertrophy and heart failure2

    • Difficulty coordinating chewing and swallowing2,3
    • Auditory nerve compression2,3
    • Optic disc swelling2,3
    • Gastrointestinal tract neuropathy leading to chronic diarrhoea2,3
    • Carpal tunnel syndrome3
    • Seizures3
    • Fine motor skill impairment3
    • Communicating hydrocephalus3
    • Spinal cord compression, which leads to muscle weakness and loss of sensation (dysaesthesia)3
    • Recurrent ear infections: acute and chronic2
    • Progressive hearing loss (due to conductive/mechanical ear symptoms such as otitis media, middle ear effusion or tympanic membrane perforation, sensorineural* problems, or a mixture of both)2

    * Resulting from neuronopathic causes

    • Enlarged tongue, tonsils and adenoids2
    • Enlarged epiglottis2
    • Difficulty with swallowing and chewing2
    • Irregular or peg-shaped teeth, with possible delayed eruption2
    • Hyperplastic or hypertrophic gingival tissue2
    • Short stature and claw-like hands2
    • Stiffened joints (due to abnormal bone thickening and joint contractures)2
    • Bulky clavicles, thickened and abnormally shaped ribs2
    • Toe-walking due to tight heel cords2
    • Irregular epiphyseal ossification of the joints in the hands, shoulders and elbows, notching on the lateral surfaces of vertebrae, destructive hip arthropathies, and eventually spinal cord deformities3,4
    • Upper airway obstructions (due to enlarged tongue, tonsils and adenoids, constricting skeletal changes in the jaw and neck, tracheal and pharyngeal deformities, mucosal thickening, abnormally shaped and stiff ribs, and constricted rib motion)3
    • Upper and lower respiratory tract infection3
    • Sleep apnoea2
Find out more about how the wide range of symptoms are managed by a multidisciplinary medical team

Disease progression

There isn’t a typical disease course in Hunter syndrome, as each individual has their own unique set of genetic mutations contributing to the disease.2

However, progressive decline is inevitable in Hunter syndrome as GAGs accumulate. Although there isn’t a typical disease course, there are common trends in the progression of the disease.2


Remember – if you suspect Hunter syndrome: REFER TO A SPECIALIST TODAY

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