Supplementary Material for: Prenatally Diagnosed De Novo Interstitial Duplication in 2p21p24.3 with Unique Manifestations: Case Report

Introduction
Partial duplications involving chromosome 2p are rare genomic events associated with variable phenotypic outcomes, ranging from craniofacial abnormalities, organ malformations to developmental delays. Prenatal identification of such duplications has become increasingly common with advances in chromosomal microarray technology, but predicting postnatal manifestations remains challenging. This report presents a de novo 32 Mb duplication of 2p21p24.3, detected prenatally, in a male infant who demonstrated unique clinical features and multisystem involvement postnatally.
Case Presentation
A 29-year-old pregnant female was referred for genetic evaluation following prenatal detection of flat nasal bridge, frontal bossing, short extremities, small penis and suspected hypospadias. Chromosomal microarray analysis revealed a 32 Mb duplication of 2p21p24.3, confirmed as de novo by parental testing. Postnatally novel features such as subglottic hemangioma, preauricular pit, and behavioral symptoms related to facial contact were noted. Growth delay, craniofacial dysmorphism, congenital heart defects, and genital anomalies were also observed.
A multidisciplinary approach involving clinical genetics was critical for addressing the patient’s complex medical needs. Despite ongoing supportive care, the patient continues facing significant developmental and medical challenges, underscoring the need for long-term follow-up as well as genotype-phenotype correlations.
Conclusion
This case broadens the clinical spectrum of partial trisomy 2p by documenting unique features, including subglottic hemangioma, behavioral symptoms and preauricular pit. It highlights the value of integrating prenatal diagnostics with detailed postnatal phenotypic assessment to improve understanding of genotype-phenotype correlations in rare chromosomal duplications. Although the PPP1CB gene within the region is might considered a plausible candidate for explaining the some of the patient’s cardinal features, dysmorphism(prominent forehead, preauricular ear pits, low-set, posteriorly rotated ears), cardiac-neurological problems, other genes associated with defined syndromes—whose clinical manifestations overlap to varying degrees—were also considered as potential contributors to the clinical picture, such as MYCN, DNMT3A, DPYSL5, and SOS1. These insights can aid clinicians in genetic counseling, anticipatory guidance, and management of similar cases in the future.

引言
涉及2号染色体短臂（2p）的部分重复是一类罕见基因组事件，其表型结局存在显著异质性，可表现为颅面部畸形、器官发育异常乃至发育迟缓。随着染色体微阵列技术（chromosomal microarray technology）的发展，此类重复的产前检出率日益升高，但预测其产后表型仍颇具挑战。本报告描述1例产前检出的新发32 Mb 2p21-p24.3区域重复病例，该男婴产后出现独特的临床特征及多系统受累表现。

病例报告
1例29岁孕妇因产前超声检出扁平鼻梁、额部隆起、肢体短小、小阴茎及疑似尿道下裂，前来接受遗传学评估。染色体微阵列分析显示其胎儿存在32 Mb 2p21-p24.3区域重复，经亲本检测证实为新发变异。产后随访发现该男婴出现声门下血管瘤、耳前窦道及与面部接触相关的行为症状等新增临床特征，同时合并生长迟缓、颅面部畸形、先天性心脏病及生殖器异常。
采用涵盖临床遗传学的多学科诊疗模式对满足该患者复杂的医疗需求至关重要。尽管已给予持续支持治疗，该患者仍面临严重的发育及医学挑战，这凸显了长期随访以及开展基因型-表型关联研究的必要性。

结论
本病例记录了声门下血管瘤、行为症状及耳前窦道等独特临床特征，拓展了2p部分三体综合征的临床表型谱。本研究强调了将产前诊断与详细的产后表型评估相结合的价值，有助于加深对罕见染色体重复病例基因型-表型关联的认识。尽管该区域内的PPP1CB基因可被视为解释患者部分主要临床特征的潜在候选基因，但患者的畸形面容（前额突出、耳前窦道、低位后旋耳）、心脏-神经系统病变，以及与已知综合征（其临床表型存在不同程度重叠）相关的其他基因——如MYCN、DNMT3A、DPYSL5及SOS1——也被认为是临床表型的潜在致病因素。上述研究结果可为临床医师开展遗传咨询、预见性指导及未来类似病例的诊疗提供参考。