CASE 17332 Published on 25.06.2021

Waardenburg syndrome


Paediatric radiology

Case Type

Clinical Cases


Dr. Foram Gala, Dr. Rohan Khadtare

Department of Radiology and Imaging, Bai Jerbai Wadia Hospital for Children, Parel Mumbai, 400012


18 months, male

Area of Interest CNS, Neuroradiology brain ; Imaging Technique MR
Clinical History

An 18-month-old male child presented with decreased movement of right upper limb and unable to hold objects. There was also history of delayed walking. On clinical examination, right upper limb power was 3/5, while power in rest of limbs was >4/5. Deep tendon reflexes were present. On clinical examination, the child's irises were noticeably bright blue colour and he also had hearing issues for which Brain evoked response analysis (BERA) was done which was suggestive of bilateral profound hearing loss.

Imaging Findings

On Magnetic Resonance Imaging (MRI), gliosis with ill-defined FLAIR hyperintense signal was seen in the left periventricular white matter and corona radiata with ex vacuo dilatation of left lateral ventricle. The child had normal birth history and no other significant post-natal ischemic event. Dedicated MRI imaging of the internal acoustic meati was also performed in view of hearing loss. It showed flattening of apical and middle turns of both cochlea with large vestibules. All the semi-circular canals appear smaller in diameter with thick arch in bilateral lateral semi-circular canal and the bony island was very small. The superior semi-circular canal on left side was not completely formed and small deformity was seen along the superior aspect of vestibule suggestive of Superior semicircular canal (SCC) anlage. Both the parotid glands also showed hypoplasia.



Waardenburg syndrome (WS), characterised by deafness and pigmentation abnormalities, is a heterogeneous genetic disorder that may be detected at birth or later in early childhood. Symptoms and features associated with it can vary from case to case; however primary features often include distinctive facial abnormality; that is hypopigmentation of the hair, skin and iris of both the eyes. Other pigmental abnormalities include white forelock, premature greying of hair, heterochromia irides and leukoderma.

WS is subdivided into different types depending upon the symptoms and genetic findings. Waardenburg syndrome type 1 is associated with dystopia canthorum (wide nasal bridge with an increase in intercanthal distance) which is not seen in Waardenburg syndrome type 2. Sensorineural hearing loss is more severe in WS type 2. Waardenburg syndrome type 3 is associated with facial, ocular abnormalities and is a more severe form of type 1. In addition, WS type 3 has joint contractures, syndactyly or winged scapulae.

Waardenburg syndrome type 4 also known as Waardenburg -Hirschsprung disease as it is associated with aganglionic megacolon. Several genes are known to cause this syndrome (PAX3, MITF, EDN3, EDNRB, SOX10), with PAX3 mutation causing type 1 and 3 WS, MITF mutation causing most of type 2 WS. However, SOX10 mutations cause approximately 15% of type 2 WS and >50 % of type 4 WS [1]. Most types are autosomal dominant in inheritance. Sox 10 mutation in type 2 WS is also associated with neurological manifestations like developmental delay, nystagmus, white matter abnormalities or hypomyelination, anosmia due to missing olfactory bulb. Pathophysiology of the depigmentation includes abnormal distribution of neural crest-derived melanocytes during embryogenesis resulting in a patchy area of depigmentation[2]. Incidentally, it is seen, that there is an absence or hypoplasia of the parotid gland [3].

Clinical Perspective

Clinically the patients present with distinctive facial abnormalities as described earlier, additionally the patient with dystopia canthorum (WS types 1 and 3) usually have a low opening of the lacrimal ducts leading to multiple episodes of dacryocystitis. The patients with dystopia canthorum show wide nasal bridge and hypoplastic nasal alae, rarely affected individuals have hypertelorism. Congenital bilateral sensorineural hearing loss is seen in almost all cases, most severe in type 2 and type 4 when associated with SOX 10 mutation.

Imaging Perspective

MRI and CT scan helps in diagnosis of inner ear abnormalities and are done as part of pre cochlear implant evaluation. Most often temporal bone abnormalities are bilateral. Usually the patients with SOX 10 mutation present with agenesis/hypoplasia of one or more semi-circular canals, more commonly posterior semicircular canal. Other findings include enlarged vestibules, flattened cochlea with occasionally abnormal shaped cochlea, absence of cochlear nerve. Additional features that can be seen are hypoplasia of the parotid glands, hypoplasia or absence of lacrimal glands, agenesis of the olfactory bulb/bulbs and white matter signal abnormalities [3].  Our patient, in addition also showed gliosis with white matter volume loss in the left periventricular white matter with ex vacuo dilatation of left lateral ventricle though he had no significant birth history or postnatal ischemic event. Since the deficit was chronic, we postulate this to be of perinatal aetiology and unrelated to WS.


Cochlear implants help to correct the profound hearing loss and in the rate of language acquisition enables development of spoken language and ultimately improves literacy in deaf children.

Take-Home Message / Teaching Points

It is important to diagnose hearing loss at an early age. These constellations of findings i.e. blue iris, profound hearing loss with characteristic inner ear abnormalities and hypoplastic parotid glands, Waardenburg syndrome must be considered. CT scan and MRI are essential in their diagnosis and in pre cochlear evaluation.

Differential Diagnosis List
Waardenburg syndrome.
CHARGE syndrome.
Vogt-Koyanagi-Harada syndrome.
Down syndrome.
Goldenhar syndrome.
Final Diagnosis
Waardenburg syndrome.
Case information
DOI: 10.35100/eurorad/case.17332
ISSN: 1563-4086