The patient was a 3-year-old female born to non-consanguineous parents, a 34-year-old father and a 38-year-old mother (Figure ). She was born at 39 weeks and 4 days gestation by normal vaginal delivery following an uneventful pregnancy. Her birth weight was 2988 g (−0.3 SD), and she measured 50.5 cm (0.4 SD) in height, with an occipitofrontal circumference (OFC) of 32 cm (−0.7 SD). Deformity of the feet was noted at birth. The left second, third, and fourth toes showed cutaneous syndactyly, and the right second and third toes showed syndactyly. An increased volume of subcutaneous adipose tissue in the left chest, the perineum, and the inside of the right thigh was obvious at one week after birth. The entire left leg and the right foot were severely enlarged, and the toes of both feet showed dactylomegaly (Figure and Figure ). Brain magnetic resonance imaging at one month showed normal findings. The patient was diagnosed with bilateral dactylomegaly at 9 months and subcutaneous adipose tissue at the left knee and the distal phalanx of the first, second, and third left toes were surgically removed. At 2 years and 9 months, subcutaneous adipose tissue at the left knee, lower abdomen, perineum, and left lower leg was surgically removed. She showed normal milestones of head control at 3 months, sitting up at 5 months, and walking at 1 year. At 2 years, her weight, height, and OFC were 12.5 kg (0 SD), 85 to 89.5 cm (−1.4 SD∼0 SD, because of different sizes of the legs), and 46.5 cm (−1.1 SD), respectively. It was noted that she had sparse hair and that her skin was thin with a small volume of adipose tissue on parts of the body other than the regions of overgrowth. Intellectual development was normal as per age equivalency and development quotient at 2 years and 4 months was 111. The presented patient was diagnosed with PROS taking into account the following findings: 1) presence of somatic PIK3CA mutation (described below), 2) congenital onset, 3) overgrowth being sporadic and mosaic, 4) overgrowth in adipose and skeletal tissues, 5) isolated macrodactyly, overgrown splayed feet, and overgrown limb, and 6) truncal adipose overgrowth []. According to Martinez-Lopez et al. [], this patient is categorized as CLOVES syndrome of PROS.
It is a 13-year-old boy born as only child from healthy non-consanguineous parents. He was born at 38 weeks of gestational age. Maternal preeclampsia was detected in the last month. Growth parameters at birth were: weight 3,880 g (+2.5 Standard deviation (SD)), length 54 cm (+3 SD), and Occipital frontal circumference 38.5 cm (+4.5 SD). No facial dysmorphisms were evident at birth. He showed mild respiratory distress, treated with oxygen support in incubator for few hours, transient hypoglycemia, requiring early oral feeding, and jaundice, treated with phototherapy.\nNormal acquisition of milestones was reported with exception of mild delay in independent walking. The patient hold up the head at 4 months, he sat unsupported at 7 months, and began walking independently at age 18 months. He started speech therapy at the age 3 years due to language delay. The first formal neuropsychological test was assessed at 11 years (WISC IV), showing a total IQ of 55, with language subitem being the worst skill. He attended the secondary school with support. He has fluent language, can read and write well. He is quiet and sociable, no behavioral problems and Autism spectrum disorder were reported. He never had seizures. As a child, at age 2 years, he suffered from viral infection with myocarditis and transient hepatosplenomegaly that spontaneously resolved after 6 months. Periodic ultrasound examination of heart, kidneys, and thyroid gave normal results. Endocrine evaluations, including Follicle-stimulating hormone, Luteinizing hormone, Thyroid-stimulating hormone, FT4-FT3, testosterone, and IGF1, gave normal results. Kidney and liver function were normal. Growth profile in term of weight and height was always harmonic and above normal ranges for Centers for Disease Control and Prevention's growth charts (respectively, weight at +3.5 SD and height at 4 SD), whereas Occipital frontal circumference measure progressively increased till +8 SD at the age of 10 years. A bone age study was performed at 7 years of age, showing mild advanced bone age (8 years). At age 12 years, weight was 80 kg (+3.6 SD), height 180 cm (+4 SD), Occipital frontal circumference 66.5 cm (+8 SD).\nHe was presented with trunk hypotonia and minor facial anomalies (Figure ). Pectus excavatum, mild joint hyperlaxity (Beighton score 3/9), and moderate scoliosis treated with corset, were also present. He underwent dermatological examination and dermoscopy because of multiple small acquired nevi. The only atypical lesion was surgically excised, and diagnosed as dysplastic Clark nevus. A small hyperkeratotic lesion on the foreskin of about 3 mm in diameter was present from birth. Brain CT scan performed at age 2 years, due to macrocephaly, showed hypodensity of the bilateral posterior periventricular white matter, and mild asymmetric lateral ventricle enlargement. Brain MRI at 12 years showed a Chiari malformation type I with right cerebellar tonsillar ectopia 12 mm below mcRae's line and mild lateral ventricular asymmetry without hydrocephalus. Symmetric megalencephaly without polymicrogyria was diagnosed.