Patient 3, a 10-year-old boy, was born by normal delivery. His parents did not show cutaneous anomalies. He was admitted for consultation due to episodes of generalized tonic-clonic seizures lasting several minutes: seizures had started at age 2 years. He showed neurodevelopmental delay from his first months of life: his current school performance is poor. An electroencephalographic (EEG) examination revealed spike and wave discharges in the temporal and parietal regions. Treatment with sodium valproate substantially reduced the frequency of seizures. At physical examination, he weighted 34 kg, with a height of 141 cm (75th percentile). The hypopigmented lesions were localized in the thorax and in the back, mainly on the left side. The diameter of the sural region of the lower left limb was 8 cm larger than the contralateral, and the diameter of the biceps region of the left limb was 3 cm larger than the contralateral. The left lower limb was 2 cm longer than the right. The asymmetry involved also the left hemiface. A lower-limb MRI showed increased growth in both long bones and soft tissues. Mild thoracolumbar right kyphoscoliosis was noticed. Brain MRI and ophthalmologic examination were both normal.
Patient 4, a 15-year-old girl, was the only daughter of nonconsanguineous parents. Both her parents were healthy with no cutaneous anomalies. The girl was born at 40 weeks by normal delivery, with a birthweight of 3300 g, a height of 50 cm, and a head circumference of 35 cm. She first came to our observation at the age of 2 years, due to psychomotor delay. The parents noticed the presence of cutaneous spots at about 3 months of age. Since her first year of life, the girl showed mild body asymmetry. At physical examination, at age 2 years, the girl showed typical hypopigmented lesions along the lines of Blaschko, mainly in the trunk and the upper and lower limbs (particularly evident over the right part of the body). During these years, the girl manifested moderate cognitive delay, poor school performance, and generalized tonic-clonic seizures, with a frequency of 6 to 8 episodes per year despite valproate treatment. At the age of 6 years, clobazam was added to the valproate regimen and the frequency of seizures decreased. An EEG revealed generalized spike and wave discharges. Currently, her physical examination reveals a weight of 70 kg and a height of 174 cm (both falling in the 90th percentile). Her school performance remained poor. The diameter of the biceps region of the right limb was 3 cm larger than the contralateral. Her right thigh diameter was 66 cm and her left thigh diameter was 57 cm (Figure ): the sural right lower limb diameter was 43 cm, compared with the left, which measured 40 cm. The right lower limb length was 103 cm, whereas the left was 100 cm. Facial asymmetry was also present, but to a milder degree. She currently walks with unstable equilibrium with frequent falls down. A color Doppler ultrasound examination of her limbs showed normal laminar flow, with a wider diameter of the arteries in the affected right limb (Figure A and B). Brain MRI was normal as her ophthalmological examination. Spinal x-ray examination revealed mild left kyphoscoliosis. Skin biopsy was not performed.