We report a child of tuberous sclerosis with a rare association of
congenital lymphedema and cardiac rhabdomyoma since birth.
A 3-month-old female child, born of
non-consanguineous marriage , was detected soon after birth to have
nonpitting edema of left lower limb extending from thigh to foot.
Neurosonogram and USG abdomen were normal. Echocardiography revealed a 9
x 9 mm rounded pedunculated mass in LV outflow tract, attached to aorto-mitral
continuity junction. Physical examination revealed multiple
hypopigmented macules in right upper limb and trunk suggestive of ash
leaf macules. X-ray chest and ECG was normal for age. Blood
investigations were normal. The child’s father had a history of seizure
disorder and was on antiepileptic drugs. His physical examination
revealed hypopigmented to depigmented macules in both upper limbs and
trunk, skin colored plaques with irregular border in lumbosacral region
and multiple hyperpigmented to erythematous papules and small plaques
over face suggestive of ash leaf macules, shagreen patches, and
angiofibromas respectively.
Lymphedema is a chronic tissue swelling that is most
commonly manifested in a limb. This condition results from impaired
lymph drainage in the presence of normal capillary filtration. The three
main consequences of lymphatic failure are lymphedema, infection and,
very rarely, cancer [1]. Most forms of primary lymphedema are thought to
be caused by a congenital abnormality of the lymphatic system and
present at or soon after birth. Cardiac rhabdomyomas are intracavitary
or intramural tumors that are present in nearly 50 to 70% of infants
with tuberous sclerosis (TSC). Most children are asymptomatic. Symptoms
are attributed to the presence of intracardiac obstruction, myocardial
involvement, and rhythm disturbances [2].
Congenital lymphedema is a rare association with
tuberous sclerosis with only few cases reported earlier [3,4]. The
previous reported patients were females but unlike our child, they
presented with history of multiple seizures while our child had no
seizures but instead had a cardiac rhabdomyoma detected incidentally. It
is interesting to note that pulmonary lymphangio-myomatosis seen in
tuberous sclerosis similarly occurs only in women which is hypothesized
to be due to the fact that estrogen regulates TSC gene signalling and,
perhaps, also the migration of TSC2-deficient cells [3].
The pathophysiology of congenital lymphedema in
tuberous sclerosis is yet unclear. Previous authors have suggested that
it could be due to the dysplastic development of lymphatic system in the
affected limb as part of TSC gene mutation as this gene regulates cell
growth, proliferation and migration. Congenital lymphedema may also be
due to the abnormal smooth cell hypertrophy in subcutaneous tissue which
externally compresses the superficial lymphatics. An increased awareness
of this association may help pediatricians suspect tuberous sclerosis in
a female child when congenital lymphedema is the sole external
manifestation.
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congenital lymphedema to the 5q35.3 region; Am J Hum Genet.
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2. Crino PB, Nathanson KL. The tuberous sclerosis
complex. N Engl J Med. 2006;13;1345-56.
3. Voudris KA, Skardoutsou A, Vagiakou E. Tuberous
sclerosis and congenital lymphedema. Pediatr Dermatol. 2003;20:371-2.
4. Lucas M, Andrade Y. Congenital lymphedema with
tuberous sclerosis and clinical Hirschsprung disease. Pediatr Dermatol.
2011;28;194-5.