Dr Joepaul Joy; Dr Sheela Namboothiri, Dr Dhanya(Genetics), Dr C Jayakumar
Nine month old male child, second born of a non-consanguineous marriage presented to Genetics OPD with the complaints of increased size of right upper limb since birth,swelling over right chest wall since last 3 days and swelling over left forearm since 1 day.
No history of injuries or fever . Term ba delivered via LSCS with birth weight of 4.1kg and cried immediately after birth. Antenatal and postnatal period were uneventful, no history maternal diabetes. He is developmentally normal and immunized for age.
On examination, child is alert.
Vitals were stable.
His weight is 9.1kg, Length-66cm, HC-45cm. Child had bluish soft tissue swelling over right chest wall, hard swelling over left forearm and right forearm hypertrophy.
Upper arm girth- 4cm more on right side
Forearm girth- 3cm more on right side
Mid thigh girth- 1cm more on left side
Child also had hypertrophy of index, middle and little finger of right hand; hypertrophy of thumb and index finger of left hand and lateral deviation of little finger of right hand.
Differential diagnosis
PIK3CA Mosaic
Tuberous sclerosis were considered.
INV
Xrays of right and left upper limbs, pelvis
and chest were taken and was normal.
ECHO and USG Abdomen were normal.
AFP was 11.73ng/ml.
WES in blood was normal.
Muscle biopsy from hypertrophied area
showed 9.2% cells with novel gain of function mutation in PIK3CA.
Child was started on Tab Sirolimus(1mg) ¼ BD. He is on Sirolimus since last one year. Current Sirolimus level is 0.98(4-6 mcg/L) and the dose is increased to 3/4thBD. There is no growth of the limb after the starting of sirolimus. Child is being followed up , counts and LFT is done regularly.
PIK3CA related overgrowth spectrum(PROS) of genetic disordersleads to overgrowth of various parts of the body due to changes (mutation)in the gene PIK3CA.
This gene is involved in making a protein that helps regulate cell growth, division and survival.
Different tissues may be involved individually or in combination such as fat, muscle, bone, nerve, brain and blood vessels.
Genetic mutations that cause these disorders are not passed down from parent to child but instead result from changes to genes during development in the womb.
Symptoms can be present at birth or appear later in childhood. Extensive or involved lesions are usually treated with drugs designed to slow down or turn off the hyperactivity of the P13K enzyme and the P13K/Akt/mTOR pathway.
Alpelisib was approved in 2022 FDA as treatment for severe cases of PROS in adults and children of 2 yrs and older.
Take home message: Hypertrophy of any part of the body during birth definitely requires a detailed genetic evaluation.