Blindness in tuberous sclerosis A case report

Niger J Paed 2015; 42 (4):346 - 349

CASE REPORT

Olaosebikan RR

Blindness in tuberous sclerosis: A

Ademola-Popoola DS

Yusuf AS

case report

Oyinloye OI

Ernest SK

Olorunsola B

Ayeni AS

Oladele DM

DOI:http://dx.doi.org/10.4314/njp.v42i4.12

Accepted: 24th June 2015

Abstract :

Tuberous

sclerosis

in the right and left eye respec-

(TS) is inherited as an autosomal

tively, both eyes had brisk pupil-

Olaosebikan RR

(

)

dominant trait with variable pene-

lary activities, good mydriasis and

Ernest SK, Olorunsola B, Ayeni AS

trance characterised by glial cell

clear media. The retinal and optic

Oladele DM

Department of Paediatrics,

tumor which arises from the cere-

nerve head appeared normal in the

bral and the retina. Blindness in

right eye whereas in the left eye

Yusuf AS

association with Tuberous sclero-

was

a huge tuberous hamartoma

Department of Surgery

sis (TS) is rare. When visual loss

of the optic disc and macular as

occurs it may be associated with

well as generalised vascular occlu-

Ademola-Popoola DS

hamartomas from retinal or optic

sion and subretinal fluid.

Department of Ophthalmology

nerve involvement or from intrac-

The Computerized tomography

ranial (brain) tumours that affect

(CT) scan showed an Intraven-

Oyinloye OI

either the part of the brain that

tricular tumour, with calcification

Departments Radiology

University of Ilorin Teaching Hospital

processes visual information or

within the tumours and subependy-

Email: laoshrsk@yahoo.com

from optic nerve damage follow-

mal. There was associated obstruc-

ing raised intracranial pressure.

tive hydrocephalus. Patient was

Very few cases of TS with blind-

managed by a multidisciplinary-

ness have been reported globally.

team of ophthalmologists, neuro-

Deterioration in academic per-

surgeons and radiologists, co-

formance might be the first

ordinated by a paediatrician.

pointer to the visual impairment.

Conclusion: The diagnosis of tu-

We report a case of a 13 year old

berous sclerosis complex (TSC)

girl who presented with increasing

was based on the lesions found on

number of facial rash over an

clinical examination, imaging, and

11years period, recurrent head-

pathologic studies. The blindness

ache and deteriorating academic

was multi-factorial in cause in-

performance of 1year and loss of

cluding intracranial, retinal and

vision of 6months with a recent

optic nerve tumours. Comprehen-

episode of convulsion. Similar

sive medical history, detailed

skin rashes without other associ-

physical examinations and neuroi-

ated symptoms were noticed on

maging study are essential in mak-

the mother and one of the younger

ing a diagnosis of TSC. Our pa-

siblings.

tient was mis-diagnosed at various

She was a Tanner stage one in

health facilities for many years.

development. She had facialan-

This delay in making appropriate

giofibromas,

shagreen patches

diagnosis and instituting treatment

over the left hypochondria, back

could have contributed to the even-

regions and face. Ophthalmic

tual outcome.

evaluation showed a visual acuity

of being able to count fingers at

Keywords:

Tuberous sclerosis,

not more than one meter from the

blindness, deteriorating academic

face and only perception of light

performance,

Introduction

cutaneous syndrome characterised by development of

hamartoma in virtually all organs in the body, com-

Tuberous sclerosis complex (TSC) is an inherited neuro-

monly in the skin, brain, lung, bones, kidney and the

347

eyes . TSC is inherited as an autosomal dominant trait

Deterioration in academic performance accompanied a

with variable penetrance and a prevalence of 1 in 6,000

progressive loss of vision in both eyes. No personality

to 10,000 individuals . The earlier in life a patient pre-

change or excessive weight changes was noticed. She

sents with symptoms and signs of tuberous sclerosis the

had an episode of generalized tonic convulsion that

greater is the like hood of mental retardation. TSC is

lasted about 20 minutes with no loss of sphincter control

associated with various types of intracranial tumours

four days prior to presentation.

including cortical tubers, subependymal nodules and

The growth and development were normal, she was

glial cell tumours. Intracranial tumours can have differ-

fully immunized according to NPI schedule. She is the

ent presentations ranging from recurrent headache,

first of the four children in a monogamous setting.

blindness or seizure. Comprehensive medical history,

She had a weight of 37 kg and occipito-frontal diameter

detailed physical examinations and neuroimaging study

of 57 cm. No lymph node enlargement, digital clubbing,

are essential in making a diagnosis of TSC. We present

or abnormal nail changes on examination of the centre

this 13 year old whose TS was not diagnosed until she

nervous system. She was well oriented in place, time

had significant life threatening deterioration and loss of

and person. Short and long term memory was intact. No

vision in both eyes.

cranial nerve palsy; power, tone and reflexes were nor-

mal. No evidence of cerebellar lesions.

Case presentation

Ophthalmic evaluation showed a visual acuity of being

A 13 year old girl presented with increasing number of

able to count fingers at not more than one meter from

facial rash over an 11year period, recurrent headache

the face and only perception of light in the right and left

and deteriorating academic performance of 1year and

eye respectively, both eyes had brisk pupillary activities,

loss of vision of 6months. There was a recent episode of

good mydriasis and clear media. The retinal and optic

convulsion. Similar skin rashes without other associated

nerve head appeared normal in the right eye whereas in

symptom were noticed on the mother and one of the

the left eye was a huge tuberous hamartoma of the optic

younger siblings. The facial rashes were initially flat and

disc and macular as well as generalised vascular occlu-

dark but subsequently became raised, dark and wider in

sion and sub-retinal fluid.

circumference.Other rashes of various sizes were no-

Prior to presentation at our facility she had been man-

ticed after births on the abdomen, back and thighs, these

aged as a case of typhoid at various private health facili-

became coalesced to form a raised roughen edge as the

ties for about one year when she presented with the

child grew.

same clinical presentation.

The rashes were dark, firm small nodules, 1 – 5 mm di-

ameter symmetrically distributed over the malar region.-

Investigations

Figure 1. There were shagreen patches over the left

hypochondria and back regions. There were no ash leaf

Serum electrolytes, urea and creatinine were essentially

spots or areas of lightening on skin. There is a similar

normal, the ECG showed sinus tachycardia with left

rash in mother noticed since childhood and in a 7 month

ventricular hypertrophy. Abdomino-pelvic ultrasonogra-

old sibling.

phy revealed bilateral kidney enlargement with multiple

Recurrent frontal, throbbing headache lasting about

hyper-echoic foci and evidence of increased vascularity

three hours twice a week, relievable by analgesia was

noticed in the preceding year prior to admission. There

Computerized tomography (CT) scan of the brain (Fig 3

was occasional photophobia and effortless vomiting

& 4) showed hyper dense lesion on left orbit, a huge

containing recently ingested food. She had no family

supratentorial mass crossing the midline, projecting into

history of migraine.

the lateral ventricle with associated dilatation. Also,

there were intraventricular tumours arising from the 3rd

Fig 1: Tuberous sclero-

ventricle extending to the anterior horn and body of the

sis characteristic le-

lateral ventricle. The CT scan also revealed calcification

sions on the face: facial

within tumours and subependymal area with associated

angiofibromata

obstructive hydrocephalus. Repeat CT scan 7 months

‘adenoma sebaceum’,

after a Ventriculo-Peritoneal (VP) shunt showed dilated

lateral ventricles with massive enlargement of the

subependymal tumours projecting into the lateral ventri-

cles

Fig 2A: Roughened,

raised lesion with an

orange peel consistency

on the left hypochon-

drial region:The Sha-

green patches.

348

Fig 4: Repeat CT scan showing huge tumour with dilatation of

MRI in the sub-region . Our patient presented with dete-

the ventricles secondary to obstruction of CSF drainage

riorating vision and deteriorating academic performance.

Tumour involving the optic nerve and the retina consti-

tute the major ophthalmic manifestation of TSC. Retinal

and nonretinal findings have been documented in

TSC . The nonretinal finding include eyelid angiofibro-

4,5

mas, strabismus, cataracts, colobomas, and iris depig-

mentation .

Tuberous sclerosis is inherited as an autosomal domi-

nant inheritance with a variable penetrance. Our patient

demonstrated this familial inheritance with two other

Fig 5: Brain CT scan showing calcified lesion on the retina

family members, the mother and one of the siblings,

presenting with classical facial manifestations of ade-

noma sebaceous. Variable expressivity is a recognised

characteristic of Tuberous sclerosis . TSC is a neurocu-

6,7

taneous disorder that is associated with tumours in vari-

ous body organs especially the brain and the kidney .

The clinical manifestation of TSC varies with age of

patients and also on the affected organs. Our patient

presented with recurrent headache, convulsion, deterio-

rating vision with eventual blindness, and decline in

academic performance. These are manifestations of cor-

Management of the patient was by a multidisciplinary

tical tumours. CNS tumours are found in 5% to 15% of

team involving the paediatrician, neurosurgeon, ophthal-

patients with TSC. These tumours differ in their loca-

mologist and the radiologist. A case review and manage-

tion, radiological characteristics, and biological behav-

ment of the patient involving all the above specialists

iour Subependymal nodules are present in almost 80%

was conducted and a joint decision on the definitive

of patients and can be identified prenatally or at birth.

management taken. On the 16th day of admission pa-

They are commonly low-grade dysplasia, which share

tient had bilateral ventriculo-peritoneal shunt (V-P

histology with subependymal giant cell astrocytoma,

shunt) done which was well tolerated. The option of

whose presentation may vary from totally asymptomatic

tumour removal cannot be done in our facility. Head-

to obstructive hydrocephalus and death.

ache subsided and vision improved. The V-P shunt

helped to decompress the brain and reduced the tension

created by the accumulated CSF. Patient was discharged

There are diagnostic criteria that have been approved for

home for follow up.

the diagnosis of TSC (Table 1). The diagnostic criteria

are the outcome of a consensus conference organised by

Seven month after the V-P shunt, her condition deterio-

the National Institute of Health in 1998 to standardize

the diagnostic criteria for TSC . Clinical manifestations

rated with evidence of raised intracranial pressure from

which she died.

and radiologic features are used in this diagnostic crite-

ria. A diagnosis of TS is made if a patient has two of the

major criteria or one major or two minor criteria (Table

1).

Discussion

Table 1: Diagnostic Criteria for Tuberous sclerosis(3)

Blindness as a manifestation of TSC is not common.

Major feature

Minor feature

There was no blindness in a population based review of

Facial angiofibromas

Multiple pits in dental enamel

100 cases by Rowley . Delay in diagnosis is not unusual

Ungula or peri-ungual fibroma

Hamartomatous rectal polyps

in our environment, this reflects the general health situa-

Shagreen patch

Bone cysts

tion and health seeking behaviour in our society.

Cortical tuber

Gingival fibroma

Subependymal nodule

Nonrenal hamartoma

In this case, an established school health and in particu-

Subependymal giant cell astro-

Retinal achromic patch

lar, school eye health services would have identified the

cytoma

child early enough for a better outcome.

Multiple retinal nodular hamar-

“confetti” skin lesion

toma

The blindness in this case is believed to have resulted

Cardiac rhabdomyoma

Multiple renal cysts

primarily from the intra-cranial manifestation of the

Renal angiomyolypoma

disease with tuberous masses along the visual pathway

Definite TSC - Either two major features or one major feature

and secondary raised intracranial pressure, retinal and

plus two minor features

optic nerve harmatomas.

Probable TSC - One major plus one minor feature

There is paucity of published reports on TSC with blind-

Possible TSC - Either one major feature or two or more minor

ness in the sub-region. Most of the reported cases of

feature

ophthalmic manifestation of TSC are from Europe and

America . This is not unconnected with the prohibi-

4,5

In a resource poor environment where healthcare financ-

tive cost of diagnostic investigations like CT scan or

ing is mainly out of pocket there is a great challenge to

349

the number of diagnostic investigations that can be

physical examinations and neuroimaging study are

done. The diagnostic criteria are of great importance in

essential in making a diagnosis of TSC. Our patient was

this situation. Our patient has more than three major

mis-diagnosed at various health facilities for many

features of this diagnostic criteria (Shagreen patches,

years. This delay in making appropriate diagnosis and

facial angiofibromas, cortical tubers, subependymal as-

instituting treatment could have contributed to the even-

trocytoma) We were able to do a brain CT scan which

tual outcome.

showed evidence of massive tumours obstructing the

foramen and also compressing on the optic disc bilater-

Conflict of Interest: None

ally.

Funding: None

Conclusion

Acknowledgement

The diagnosis of tuberous sclerosis complex was based

We acknowledge all the doctors and nurses of the

on the lesions found on clinical examination, imaging,

Department of Paediatrics, University of Ilorin Teaching

and pathologic studies. The blindness was multi-

Hospital for their support during the management of this

factorial in cause including intracranial, retinal and optic

patient.

nerve tumours. Comprehensive medical history, detailed

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