P.19.6 PIK3CA somatic mutation in congenital monomelic muscular hypertrophy of the upper extremity. Case report

Congenital isolated unilateral hypertrophy of upper extremity secondary to muscular hyperplasia is a rare phenomenon of unknown etiology. There are only few reports variably defining it as an aberrant muscle syndrome or congenital monomelic muscular hypertrophy. We report the case of a 6-year old girl with a congenital enlargement of the whole left arm, and hand deformity. MRI showed a generalized enlargement given by homogenous increase in muscle bulk with no fat replacement together with aberrant muscles in the hand. No dysfunctions of the shoulder, elbow or wrist were detected. The patient presented normal development, with no cutaneous stigma nor additional features usually seen in Proteus syndrome. The left hand was wider with ulnar drift of the index finger, increased muscle bulk of the first dorsal interosseous and widening of the 2nd and 3rd metacarpal space. A muscle biopsy of the prominent tissue in the dorsal face of the hand revealed dystrophic features with abnormally increased variability of fibres together with many hypertrophic fibres associated with increased perimysial and endomysial fibrosis. Type 1 fiber predominance, and disorganization of the intermyofibrilar network was evident at histochemistry for NADH, COX and SDH. Mosaic activating mutation in the PI3K–AKT cell signaling pathway have been described in overgrowth syndromes such as Proteus syndrome, CLOVES syndrome, megalencephaly–capillary malformation, fibroadipose hyperplasia and macrodactyly. Given the relationship of mosaic activating mutations in the PI3K–AKT cell signaling pathway with other overgrowth syndromes, Sanger sequencing for AKT, PIK3CA, and PTEN was performed. A mutation c.3140A > G, p.H1047R in PIK3CA was detected in DNA from the affected muscle but not from blood leucocytes. Isolated congenital upper limb hypertrophy with aberrant hand muscles is another condition related genetically to overgrowth syndromes.