Clinical Brief

Tuberous Sclerosis – A Multi System Disease
Vijinder Arora, Inderbir Singh Nijjar, Jatinderpal Singh and P.S. Sandhu
Nijjar Scan and Diagnostic Centre, Amritsar, India

ABSTRACT
Tuberous sclerosis is a genetic disease with autosomal dominant inheritance, associated with hamartomata in several organs
and various skin findings. A case of a ten year old boy is presented here to highlight the multisystem involvement in tuberous
sclerosis. The child had seizures, facial papular naevi and periungual fibromas. MRI revealed cortical tubers, white matter lesions
and subependymal nodules. Orbital ultrasound showed retinal hamartoma on the left side. Ultrasound of the abdomen revealed
a soft tissue mass at the upper pole of left kidney with a small cyst in right kidney. [Indian J Pediatr 2008; 75 (1) : 77-79]
E-mail : dr_vijinderarora@yahoo.co.in

Key words : Tuberous sclerosis; Hamartoma; MRI

Tuberous Sclerosis (TSC) was first described in the 1880’s
as “Bourneville’s disease” named after the French
physician Desire-Magloire Bourneville (1840-1909),
tuberous sclerosis complex. It was an estimated
prevalence of 3-10/100,000 worldwide.1 It is a genetic
disorder that affects multiple organs. Skin, brain, kidney,
eyes and heart are some of the organs that may be
involved. The term ‘complex’ emphasizes the
multisystem involvement and variable expression of the
disease.2

projection was noted at the base of the nails in the left
third finger (Fig 2) and right second finger indicative of
an ungual fibroma.
He was referred for MRI of the brain, which revealed
multiple lesions in the cortex of both cerebral

CASE REPORT
A ten years old boy presented with history of seizures off
and on for the last six months. He was mildly mentally
retarded. There was no history of headache, chest pain,
shortness of breath or any urinary or bowel complaints.
He was the eldest of three siblings. The other two children
were normal. There was no family history of any such
skin lesion, fits or mental retardation. No such history
was available in the first-degree relatives also.

Fig. 1. Photograph of the patient showing papular naevus

On examination, the child was of lean built and was
well oriented in time and space and afebrile. The vital
signs were stable. There were multiple small skin
coloured papules over the nose and both cheeks
suggestive of a papular naevus (Fig. 1). A small reddish

Correspondence and Reprint requests : Dr. Vijinder Arora, M.D.
(Radiodiagnosis) Nijjar Scan and Diagnostic Centre, 51/1, Court
Road, Amritsar-143001 Punjab, India, Fax : -0183-2226633
[Received September 2, 2005; Accepted October 17, 2005]

Indian Journal of Pediatrics, Volume 75—January, 2008

Fig. 2. Ungual fibroma at the base of nail of left third finger

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V. Arora et al
hemispheres consistent with cortical tubers (Fig 3).
Multiple subependymal nodules were detected jutting
into both lateral ventricles (Fig 4).

Ultrasound of the abdomen demonstrated a small
mass of intermediate echogenecity, measuring 1.5 x 1.2cm
in size, at the upper pole of left kidney (Fig 5). A tiny cyst
was seen in the interpolar region of right kidney. No
lesion was observed in the liver or pancreas.
Ultrasound of the orbit showed a plaque like mass in
the lateral quadrant of left eyeball suggestive of retinal
hamartoma (Fig. 6).

Fig. 5. Ultrasound abdomen showing left renal cyst

Fig. 3. FLAIR axial MR section depicting cortical tubers

Fig. 6. Ultrasound of the orbit demonstrating plaque-like mass in
the lateral quadrant of left eyeball

DISCUSSION
Rayer gave the first complete description of tuberous
sclerosis in 1835.3 Sherlock4 coined the name ‘epiloia’,
which highlighted the previous diagnostic triad
composed of epilepsy, low intelligence and adenoma
sebaceum. However, the classic clinical triad is found in
less than half the patients.

Fig. 4. T1W axial MR section revealing subependymal nodules

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Onset before the age of 5 years with cutaneous
changes or with epilepsy is usual, but the disease may
remain latent until adolescence. 5 The disease shows
variable expressivity even within the same family. It is
now recognized that about half of the TSC families are
linked to chromosome 9q34 (TSC1) and the other half to
chromosome 16p13 (TSC2).6 The inheritance is autosomal
dominant.
Indian Journal of Pediatrics, Volume 75—January, 2008

Tuberous Sclerosis – A multi System Disease
Histopathologically most of the lesions are
hamartomas, and in many organs the cells resemble
embryonic cells, suggesting that the defect occurs at an
early stage of life. Most of the cutaneous lesions show
excess of collagen. The angiofibromas consist of
hyperplastic blood vessels and sebaceous glands of
immature hair follicles, in addition to increased collagen
synthesis.7
US National Tuberous Sclerosis Association has
divided the clinical features into 3 groups: primary,
secondary and tertiary.8 Primary features include facial
angiofibroma, multiple ungual fibroma, cortical tuber
(histologically confirmed), subependymal nodules or
giant cell astrocytomas, multiple calcified subependymal
nodules and multiple retinal astrocytomas. Secondary
features include an affected first degree relative, cardiac
rhabdomyoma, retinal hamartoma, cerebral tubers
(radiologically confirmed), non-calcified subependymal
nodules, shagreen patch, forehead plaques, pulmonary
lymphangiomyomatosis, renal angiomyolipomas and
renal cysts (the last two features should be histologically
confirmed). Tertiary features are hypomelanotic macules,
renal cysts (radiologically confirmed), dental enamel pits,
hamartomatous rectal polyps, bone cysts, pulmonary
lymphangiomyomatosis (radiologically confirmed) and
cerebral heterotopias, gingival fibromas, hamartomas of
other organs and infantile spasm.
For the definitive diagnosis there should be either one
primary and two secondary features or one secondary
and two tertiary features. Our patient had at least three
primary and three secondary features. All these features
are found bilaterally. There were, however, a few case
reports in which one of the features of the disease was
found unilaterally.9
The skin lesions are found in 60-70% of cases. There
are four characteristic skin lesions; angiofibromas,
periungual fibroma (Koenen tumour), shagreen patch
and ash-leaf macules. The angiofibromas are firm,
discrete, red-brown, telangiectatic papules, 1-10 mm over
nasolabial furrow, eyelids, cheek and chin. Periungual
fibromas are smooth, firm, flesh-coloured excrescence
emerging from nail folds. Shagreen patch is an irregular
thickened, skin-coloured plaque, usually over
lumbosacral region. Ash-leaf macules are ovoid, white
macules, 1-3 cm in size, present over trunk or limbs.2
Mental deficiency is seen in 60-70% of cases and may
progress. Epilepsy is seen in all mentally-retarded and

Indian Journal of Pediatrics, Volume 75—January, 2008

70% of individuals of average intelligence. Ocular signs
occur in 50% of cases, but may be hard to detect. Other
systemic abnormalities include cardiac rhabdomyomas,
renal angiolipomas, spontaneous pneumothorax and
hamartomatous colonic polyps.
The cosmetic appearance is improved by removing
angiofibromas with pulse-dye vascular laser (wavelength
585nm) or by carbon dioxide laser. Surgical treatment
may be required for relief of symptoms in other organs.2
The life expectancy of severely affected infants is poor.
Three percent die in first year, 28% under 10 years and
75% before 25 years. The prognosis for older children or
young adults with mild disease is unpredictable.2
Well conducted studies estimate that about 2/3 of
cases are fresh mutations, and the remaining cases are
familial in an autosomal dominant pattern of inheritance.
For proper genetic counseling mutation studies should be
carried out on the affected child. Both genes are studied in
sequence. Children of an affected parent should be
offered a skin examination for ash leaf spots, renal and
liver ultrasound and cardiac ultrasound at the initial
consultation.10 Prenatal diagnosis is possible with DNA
technology, provided mutation in the affected child in
known.
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