This 2-year-old boy is the second child of a healthy 27-year-old woman and a non-consanguineous 28-year-old healthy man. Their family history was unremarkable. He was conceived naturally and was born at term after an uncomplicated pregnancy: his fetal ultrasounds were normal. His birth weight was 3650 g (75th percentile), length 52 cm (75th percentile), and head circumference 33 cm (50th percentile). Postnatally, increased growth of the trunk, widespread cutaneous capillary malformations, and gigantism with exadactyly of the right hand became evident, suggestive for a complex lymphatic-arteriovenous overgrowth malformation. Upon monthly follow-up visits, weight and length growth were regular; however, subcutaneous masses (Fig. A, B) and increased growth of the hand became more evident (Fig. B: 3,5). His development was apparently normal. MRI and computerized tomographic (CT) scans revealed vascular malformations and vesicles within the masses noted in the trunk, with variable extension into the retroperitoneal and mediastinum regions; x-ray examination of the hands confirmed the skeletal exadactyly of the right hand; histological examination of the affected (and unaffected) tissues confirmed the initial hypothesis of a mixed lymphatic-arteriovenous malformation in the spectrum of CLOVES syndrome. Skin biopsies from the affected (and unaffected contralateral) regions were obtained during these procedures (Fig. b).
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.