AP-HP, Service de Génétique Clinique, Necker-Enfants malades University Hospital, Paris, France.
INSERM, UMR1163, Iimagine Institute, Paris, France.
Am J Med Genet A. 2020 Jan;182(1):29-37. doi: 10.1002/ajmg.a.61364. Epub 2019 Oct 25.
Adams-Oliver syndrome (AOS) is a genetic disorder characterized by the association of aplasia cutis congenita (ACC), terminal transverse limb defect (TTLD), congenital cardiac malformation (CCM), and minor features, such as cutaneous, neurological, and hepatic abnormalities (HAs). The aim of the study is to emphasize phenotype-genotype correlations in AOS.
We studied 29 AOS patients. We recorded retrospectively detailed phenotype data, including clinical examination, biological analyses, and imaging. The molecular analysis was performed through whole exome sequencing (WES).
Twenty-nine patients (100%) presented with ACC, the principal inclusion criteria in the study. Seventeen of twenty-one (81%) had cutis marmorata telangiectasia congenita, 16/26 (62%) had TTLD, 14/23 (61%) had CCM, 7/20 (35%) had HAs, and 9/27 (33%) had neurological findings. WES was performed in 25 patients. Fourteen of twenty-five (56%) had alterations in the genes already described in AOS. CCM and HAs are particularly associated with the NOTCH1 genotype. TTLD is present in patients with DOCK6 and EOGT alterations. Neurological findings of variable degree were associated sometimes with DOCK6 and NOTCH1 rarely with EOGT.
AOS is characterized by a clinical and molecular variability. It appears that degrees of genotype-phenotype correlations exist for patients with identified pathogenic mutations, underlining the need to undertake a systematic but adjusted multidisciplinary assessment.
Adams-Oliver 综合征（AOS）是一种遗传性疾病，其特征为先天皮肤发育不全（ACC）、末端横断肢体缺陷（TTLD）、先天性心脏畸形（CCM）和皮肤、神经及肝脏异常等轻微特征（HA）的联合出现。本研究旨在强调 AOS 的表型-基因型相关性。
我们研究了 29 例 AOS 患者。我们回顾性地记录了详细的表型数据，包括临床检查、生物学分析和影像学。通过全外显子组测序（WES）进行分子分析。
29 例患者（100%）均存在 ACC，这是本研究的主要纳入标准。21 例中的 17 例（81%）存在先天性大理石样皮肤毛细血管扩张，16/26（62%）存在 TTLD，14/23（61%）存在 CCM，7/20（35%）存在 HA，27/27（97%）存在神经学发现。对 25 例患者进行了 WES。25 例中的 14 例（56%）存在已在 AOS 中描述的基因改变。CCM 和 HA 特别与 NOTCH1 基因型相关。DOCK6 和 EOGT 改变的患者存在 TTLD。不同程度的神经学发现与 DOCK6 相关，偶尔与 NOTCH1 相关，很少与 EOGT 相关。
AOS 的特点是临床和分子的变异性。似乎存在与已识别的致病性突变患者的基因型-表型相关性的程度，强调需要进行系统但调整后的多学科评估。
