This 6-year-old girl is the third child of a healthy 42-year-old woman and a non-consanguineous 52-year-old healthy man, whose family history was unremarkable. She was conceived naturally. She was born at term after a normal pregnancy: her fetal ultrasound scans were normal. Birth weight was 3.800 g (75th centile), length 51 cm (75th centile), and head circumference 36 cm (75th centile). At birth, macrodactyly of the I and II toe of the left foot with partial syndactyly between the 2nd and 3rd toes was recorded. Based on these clinical data, she was suspected to have Proteus syndrome. At the age of 1 month, a subcutaneous mass in her left abdominal region was observed. General physical examination at age 2 months showed that her weight was 5600 g (90th percentile), length 56 cm (50th percentile), and head circumference 38.5 cm (50th percentile). She presented macrodactyly of the I and II toes of the left foot with increased growth of the left leg and a subcutaneous mass in the left abdominal region; magnetic resonance imaging (MRI) of the abdomen revealed that the mass was compatible with a subcutaneous lipoma, which was later confirmed by histological examination of a sample of biopsied tissue. The girl was first referred to one of our institutions at age 4 months and followed up at age 9 months, 3 years and 10/12 months, and 5 years; she is still under follow-up at our institutions. Cognitive development is normal. During her last diagnostic work-up and follow-up controls, she underwent surgery for reduction of the abdominal mass and for removal of the first toe and transposition of the second toe to replace the first toe. Skin biopsies from the affected (and unaffected contralateral) regions were obtained during these procedures (Fig. a).
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.