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Table of Contents    
Year : 2016  |  Volume : 64  |  Issue : 6  |  Page : 1312-1313

Commentary: Wolfram (DIDMOAD) syndrome: A progressive disorder with nonsynchronized clinical and imaging features

Department of Neurosurgery, C. N. Centre, All India Institute of Medical Sciences, New Delhi, India

Date of Web Publication11-Nov-2016

Correspondence Address:
Guru Dutta Satyarthee
Department of Neurosurgery, C. N. Centre, All India Institute of Medical Sciences, New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.193809

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How to cite this article:
Satyarthee GD. Commentary: Wolfram (DIDMOAD) syndrome: A progressive disorder with nonsynchronized clinical and imaging features. Neurol India 2016;64:1312-3

How to cite this URL:
Satyarthee GD. Commentary: Wolfram (DIDMOAD) syndrome: A progressive disorder with nonsynchronized clinical and imaging features. Neurol India [serial online] 2016 [cited 2021 May 7];64:1312-3. Available from:

The authors report the case of a 27-year-old male patient who presented with progressive visual diminution, bilateral sensorineural hearing impairment, and history of juvenile-onset diabetes mellitus; however, cranial magnetic resonance imaging (MRI) revealed paucity of neuroimaging abnormality, which was only limited to the ventral pons and optic radiation showing a hyperintense signal, despite marked endocrinal and neurological deficit. In Wolfram syndrome, the clinical and imaging findings may not always appear in synchrony, with either radiological features preceding the onset of clinical features or vice versa.[1]

Wolfram syndrome is a rare, autosomal recessive genetic disease with an estimated prevalence of approximately 1 in 770,000 people.[2] It is characterized by the presence of juvenile-onset insulin-dependent diabetes mellitus, bilateral optic nerve atrophy, diabetes insipidus, along with hearing impairment and symptoms related to the dysfunction of various regions of brain caused by degeneration.[2] Wolfram syndrome is caused by mutation of Wolfram syndrome type 1 (WSF1) gene, which is responsible for coding wolframin and maps to chromosome 4p.[3] The WSF1 gene loss causes chronic endoplasmic reticulum stress-mediated apoptosis of cells with a high secretary demand in various organs of the body, i.e., pancreatic β cells, neuronal, and endocrine cells causing diabetes mellitus, progressive neurological degeneration, and results in endocrinal dysfunction.[4]

The first manifestation is usually juvenile-onset diabetes mellitus in childhood with subsequent development of optic atrophy that occurs mostly within the first decade of life. Approximately 51–80% of the cases develop partial central diabetes insipidus and 60% of the cases develop progressive high frequency hearing loss.[5] Additional symptoms are stunting of growth, hypogonadism, hypothyroidism, and primary gonadal atrophy. Premature death is attributed to respiratory failure related to brain stem atrophy.[5] The minimal diagnostic criteria of Wolfram syndrome are juvenile-onset diabetes mellitus and bilateral progressive optic atrophy.[5],[6]

Focal neurological deficits are seen in approximately 60% of the cases and include ataxia of the trunk, impairment of gag reflex, and epilepsy.[5] Widespread abnormalities in the brain are noticed during the post-mortem pathological examination of the hypothalamus, pituitary, pons, inferior olivary nucleus, lateral geniculate nucleus, optic nerve, optic tract, and cerebellum and collectively produce the characteristic neurological and endocrine dysfunctions.[7]

Hershey et al., analyzed neuro-anatomical abnormalities on MRI in 11 cases and an age-matched cohort and reported that radiological abnormalities were present in the brainstem, cerebellum and optic radiation. This was associated with a significant volume loss of the brainstem, cerebellum, and a relatively smaller loss of intracranial compartmental volume with onset at early childhood.[7] Ito et al., reported a 35-year-old male patient who was clinically asymptomatic for brainstem or cerebellar lesions; however, MRI of the brain revealed widespread signal alterations and atrophy of the brainstem, middle cerebellar peduncle, and cerebellum.[8] Pakdemirli et al.,[3] reported the characteristic MRI brain imaging findings of Wolfram syndrome in addition to the usual signal alteration in the bilateral optic radiations and in the periventricular white matter of the parieto-occipital and temporal lobes in a 32-year-old female patient, thus further highlighting the widespread brain parenchymal involvement.[3]

  References Top

Wolfram (DIDMOAD) syndrome with ventral central pontine hyperintensity without brainstem atrophy. Neurol India, 2016;64:1310-12.  Back to cited text no. 1
Barrett TG, Bundey SE, Fielder AR, Good PA. Optic atrophy in Wolfram (DIDMOAD) syndrome. Eye 1997;11:882-8.  Back to cited text no. 2
Pakdemirli E, Karabulut N, Bir LS, Sermez Y. Cranial magnetic resonance imaging of Wolfram (DIDMOAD) syndrome. Aust Radiol 2005;49:189-91.  Back to cited text no. 3
Harding HP, Ron D. Endoplasmic reticulum stress and the development of diabetes: A review. Diabetes 2002;51(Suppl. 3):S455-61.  Back to cited text no. 4
Barrett TG, Bundey SE, Macleod AF. Neurodegeneration and diabetes: UK nationwide study of Wolfram (DIDMOAD) syndrome. Lancet 1995;346:1458-63.  Back to cited text no. 5
Rohayem J, Ehlers C, Wiedemann B, Holl R, Oexle K, Kordonouri O, et al. Wolfram Syndrome Diabetes Writing Group. Diabetes and neurodegeneration in Wolfram syndrome: A multicenter study of phenotype and genotype. Diabetes Care 2011;34:1503-10.  Back to cited text no. 6
Hershey T, Lugar HM, Shimony JS, Rutlin J, Koller JM, Perantie DC, et al., Washington University Wolfram Study Group. Early brain vulnerability in Wolfram syndrome. PLoS One 2012;7:e40604.  Back to cited text no. 7
Ito S, Sakakibara R, Hattori T. Wolfram syndrome presenting marked brain MR imaging abnormalities with few neurologic abnormalities. Am J Neuroradiol 2007;28:305-6.  Back to cited text no. 8


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