case_images: PMC10919150_01
case_images: Clinical (A-C), pathologic (D) and radiologic findings (E, F) of the case. (A) At the age of 5 years, there was severe overgrowth of the left arm, with skin pigmentation over the forearm and angiokeratomas over the hand. (B) Immediately before treatment with sirolimus (age, 7 years and 7 months), the left forearm showed marked swelling and skin pigmentation. (C) After sirolimus treatment (age, 9 years and 1month), swelling and pigmentation improved. (D) Histopathology of the resected tissue of left forearm showed vascular malformation: proliferation of lymphatic and small blood vessels, with deformation of arteries and veins and dilatation of lymphatic vessels. (E) Chest computed tomography before treatment with sirolimus (age, 7 years and 0 month) showed thickening of the pulmonary interstitium and partial emphysematous change of the lung field. (F) After sirolimus treatment (age, 8 years and 9 months), these changes improved. There is in the right lung arteriovenous malformation.
case_images: fped-12-1333064-g001.jpg
case_images: PMC10919150_01_fped-12-1333064-g001.jpg
case_images: F1
case_images: A pathological diagnosis of vascular malformation was made (Figure 1D). At 7 years of age, she showed marked overgrowth of the entire left arm, with pigmentation of the skin over the hand and forearm (Figure 1B). Chest CT showed thickening of the bronchial walls and interlobular septa in the bilateral lungs, partial emphysematous changes in the lung field (Figure 1E), and an arteriovenous fistula in the right lower lobe (S7) of the right lung. Hypertrophy and pigmentation of the left arm ameliorated markedly (Figure 1C). Chest CT showed improvement of the pulmonary lesions (Figure 1F).
case_images: Genetic analyses using SNP array using human reference genome GRCh37/hg19 demonstrated the germline and somatic mutation in this case. (A) Analysis of the peripheral blood found a heterozygous microdeletion of 9q34.13 including the TSC1 gene, with the TSC1 gene copy number being approximately one. (B) Analysis of the resected hypertrophic tissue detected isodisomy of 9q21.23-9qter, resulting in TSC1 loss of heterozygosity (LOH), with the TSC1 gene copy number smaller than one. The slight shift in the allele-specific analysis and the retention of marks indicating heterozygosity suggest mosaicism. The red plot displays the total copy number for each probe, along with the moving average indicated by a blue line. Below the cytoband, green marks signify heterozygous SNPs. In allele-specific analysis, the larger and smaller alleles are shown in red and green, respectively.
case_images: fped-12-1333064-g002.jpg
case_images: PMC10919150_01_fped-12-1333064-g002.jpg
case_images: F2
case_images: HD array (Affymetrix, Santa Clara, CA) and CNAG/AsCNAR algorithm detected in the blood a deletion of chromosome 9q34.13, from chr9;135664166 to chr9;135851161, including the TSC1 gene, and in the hypertrophic arm tissue isodisomy of 9q21.23-qter causing allelic loss of the TSC1 gene (Figure 2). Hemihypertrophy was thus demonstrated to be caused by TSC1 LOH resulting from the germline and somatic mutations.