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).
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.