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.
This 17-year-old boy was the only child born to non-consanguineous parents. His father and grandfather showed diffuse angiomatosis. He was conceived naturally. His fetal ultrasound scan showed IUGR. At birth, a diffuse capillary malformation involving the trunk and limbs was recorded. At age 3 months, he was noted to have left asymmetric overgrowth. During his follow-up visits, cardiac and abdominal ultrasound scans were repeatedly normal. Early developmental milestones were delayed, and at age 7 months, a brain MRI scan revealed focal hemimegalencephaly with right perisylvian polymicrogyria. From age 5 years, he started to manifest episodes of generalized tonic-clonic seizures, which proved to be refractory to antiepileptic therapy. He was severely cognitively impaired and developed an attention deficit disorder. On physical examination, at age 13 years and 8/12 months, his weight was 41.5 kg (10th–25th percentile), height 154.2 cm (10th–25th percentile), and head circumference 50.2 cm (2 SD < 3rd percentile). He had left asymmetric overgrowth, involving the face, trunk, and limbs (mainly the legs) with diffusely soft and thick irregularly marbled skin and prominent capillaries and veins on the trunk, abdomen, and limbs. His 2nd and 3rd left toes were significantly larger than the contralateral and showed proximal cutaneous syndactyly. Besides the increased growth, he had dysmorphic features including malar hypoplasia, long philtrum and high palate, and S-shaped scoliosis. Skin biopsies from the affected (and unaffected contralateral) skin regions were obtained.