Abstract：
Aplasia Cutis Congenita with Ectrodactyly Skeletal Syndrome (ACCES, OMIM #619959) is an extremely rare multiple congenital anomalies syndrome caused by haploinsufficiency of the UBA2 gene. This syndrome presents with growth retardation, dysmorphic facial features, neurodevelopmental delay, skeletal problems including ectrodactyly, developmental dysplasia of the hip (DDH) and scoliosis, skin findings such as aplasia cutis, and some internal organ abnormalities. Our 13-year-old female patient and her 38-year-old father had a skeletal dysplasia phenotype with disproportionate short stature, bilateral DDH, mild epiphyseal involvement, scoliosis, and increased lumbar lordosis. Both were neurodevelopmentally normal and had mild dysmorphic facial features and mild ectodermal findings. The dominant inheritance pattern in the pedigree suggested a pre-diagnosis of spondyloepiphyseal dysplasia tarda. The exome sequencing analysis of the patient has identified a novel heterozygous variant, NM_005499.2:c.460-2A >G, in the UBA2 gene, and the father was found heterozygous either. The isolated spondyloepiphyseal involvement of our patients was an unusual presentation compared to patients with ACCES syndrome previously reported in the literature. Considering the highly variable expressiveness of ACCES syndrome and the co-occurrence of familial hip dysplasia and vertebral problems, we suggest that this syndrome can also be classified under \"Spondyloepi(meta)physial dysplasia (SE(M)D)\" in the nosology of genetic skeletal disorders.
摘要：
先天性外生症伴外生性骨骼综合征(ACCES，OMIM＃619959）是由UBA2基因单倍体功能不全引起的极为罕见的多发性先天性异常综合征。这种综合征表现为生长迟缓，畸形面部特征，神经发育迟缓,骨骼问题，包括外突，发育性髋关节发育不良（DDH）和脊柱侧凸，皮肤发现，如角质层发育不全，还有一些内脏器官异常.我们的13岁女性患者和她38岁的父亲有骨骼发育不良表型与不成比例的身材矮小，双侧DDH,轻度骨phy受累，脊柱侧弯,腰椎前凸增加.两者都是神经发育正常的，并且具有轻度的畸形面部特征和轻度的外胚层发现。家系中的显性遗传模式提示了脊柱骨发育不良的早期诊断。患者的外显子组测序分析发现了一种新的杂合变体，NM_005499.2:c.460-2A>G,在UBA2基因中，父亲也被发现是杂合的。与文献中先前报道的ACCES综合征患者相比，我们患者的孤立脊柱骨epi受累是一种不寻常的表现。考虑到ACCES综合征的高度可变表达和家族性髋关节发育不良和椎体问题的同时发生，我们建议该综合征也可以归类为遗传性骨骼疾病的“Spondyloepi（meta）生理发育不良（SE（M）D）”。
