关键词: 12 q 14 微缺失综合征； 身材矮小； Silver-Russell 综合征； 染色体微阵列分析

Abstract: Objective To report a rare case of 12 q 14 microdeletion syndrome with overlapping phenotypes of SilverRussell syndrome（SRS） combined with early puberty, and to review the relevant literatures to find genotype-phenotype corelation. Methods By searching PubMed, Wanfang Medical Database and China HowNet, a total of 26 cases of 12 q 14 microdeletion syndrome were reported abroad. The clinical features and genetic change in these 26 cases and one patient diagnosed in our hospital were summarized. Results The girl is 9 years and 3 months old. Clinical features included short stature (height: 113 cm/- 3 . 6 SD; weight: 18 . 4 kg/- 2 . 1 SD; head circumference (HC): 45 cm/- 4 . 2 SD), intellectual disability, learning difficulties, patent ductus arteriosus, congenital right renal dysplasia, facial dysmorphism, scoliosis, and early puberty. Chromosome microarray analysis identified a 5 . 8 Mb deletion in 12 q 14 . 2 q 15 band. The common clinical phenotypes in 27 patients with 12 q 14 microdeletion syndrome included short stature ( 23 cases, 85 %), craniofacial malformations ( 22 , 81 %), and small for gestational age infant (SGA) ( 21 , 78 %), intellectual disability/developmental delay ( 21 , 78 %), feeding difficulties ( 15 , 55 %), delayed language development ( 12 , 44 %), learning difficulties ( 10 %), osteopoikilosis ( 6 , 22 %), congenital heart disease ( 6 , 22 %), Other clinical phenotypes included relative macrocephaly ( 5 , 18 %), scoliosis ( 4 , 15 %), and autism ( 4 , 15%). Nine of the 27 patients were diagnosed as SRS in the final diagnosis ( 33 . 3%). The HMGA2 gene was deleted in 23 patients with short stature; the GRIP1 gene was deleted in 21 patients with intellectual disability / developmental delay, 6 patients were diagnosed with osteopoikilosis with LEMD 3 gene deletion. Conclusion The most common clinical phenotype of 12 q 14 microdeletion syndrome is short stature. It is important to measure growth hormone level and pubertal signs for follow-ups with these patients to avoid consequential short statue in adulthood. Children with LEMD 3 gene deletion need to monitor bones for early detection of osteopoikilosis. Chromosome microarray analysis should be considered for patients diagnosed with idiopathic SRS, especially if they have any atypical features such as microcephaly or more severe learning problems or intellectual disability.

Key words: 12 q 14 microdeletion syndrome; short stature; Silver-Russell syndrome; chromosomal microarray analysis