X Yu1, J Zhang1, Y Gu1, D Deng1, Z Wu2, L Bao3, M Li1, Z Yao1. 1. Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. 2. Department of Dermatology, Shanghai First People's Hospital, Shanghai Jiaotong University of Medicine, Shanghai, China. 3. Department of Radiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Abstract
BACKGROUND: Congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD) syndrome is a rare X-linked dominant disorder characterized by peculiar cutaneous presentations and ipsilateral skeletal abnormalities. CHILD syndrome is caused by mutations in NSDHL gene, which involves in cholesterol synthesis. OBJECTIVES: To verify the diagnosis of CHILD syndrome and seek effective pathogenesis-based therapy with little side-effects. METHOD: We comprehensively evaluated the patient's conditions. Pathological biopsy was performed in the lesion location. Genetic tests and real-time quantitative PCR were conducted to further confirm the diagnosis. The topical application of a mixed lotion containing 2% simvastatin and 2% cholesterol to lesion areas based on the pathogenesis as well as the literature review. RESULTS: We diagnosed a rare and typical case of CHILD syndrome co-occurring with multiple VX-like lesions. The gene mutation is a large deletion of exon 3 and 4 of the NSDHL gene, which was discovered and reported for the first time in CHILD syndrome. The skin lesions, including the verruciform plaques and VX-like lesions, improved obviously after treatment. CONCLUSIONS: Multiple exons deletions or microdeletion was not rare in CHILD syndrome. Classical Sanger sequencing may not be useful enough to find all kinds of mutations. Next-generation sequencing may be more effective. It is important to conduct genetic counselling to prevent more serious defects in descendants. The excellent therapeutic effect on CHILD syndrome resulted from the topical treatment with simvastatin/cholesterol provides a proof-of-concept for other topical pathogenesis-based therapies for skin disease.
BACKGROUND:Congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD) syndrome is a rare X-linked dominant disorder characterized by peculiar cutaneous presentations and ipsilateral skeletal abnormalities. CHILD syndrome is caused by mutations in NSDHL gene, which involves in cholesterol synthesis. OBJECTIVES: To verify the diagnosis of CHILD syndrome and seek effective pathogenesis-based therapy with little side-effects. METHOD: We comprehensively evaluated the patient's conditions. Pathological biopsy was performed in the lesion location. Genetic tests and real-time quantitative PCR were conducted to further confirm the diagnosis. The topical application of a mixed lotion containing 2% simvastatin and 2% cholesterol to lesion areas based on the pathogenesis as well as the literature review. RESULTS: We diagnosed a rare and typical case of CHILD syndrome co-occurring with multiple VX-like lesions. The gene mutation is a large deletion of exon 3 and 4 of the NSDHL gene, which was discovered and reported for the first time in CHILD syndrome. The skin lesions, including the verruciform plaques and VX-like lesions, improved obviously after treatment. CONCLUSIONS: Multiple exons deletions or microdeletion was not rare in CHILD syndrome. Classical Sanger sequencing may not be useful enough to find all kinds of mutations. Next-generation sequencing may be more effective. It is important to conduct genetic counselling to prevent more serious defects in descendants. The excellent therapeutic effect on CHILD syndrome resulted from the topical treatment with simvastatin/cholesterol provides a proof-of-concept for other topical pathogenesis-based therapies for skin disease.