Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.
Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia.
Clin Dysmorphol. 2021 Apr 1;30(2):89-92. doi: 10.1097/MCD.0000000000000347.
The proband, now a 4-year-old female of mixed Caucasian and Japanese ancestry, was born at 29 weeks gestation via spontaneous vaginal delivery following a pregnancy complicated by fetal ascites, echogenic bowel, polyhydramnios, and incompetent cervix. The mother had no other pregnancy complications and had no recognized teratogen exposures throughout the pregnancy. Her length was 37 cm (37 centile), weight was 1.478 kg (80 centile), and occipitofrontal circumference (OFC) was 27 cm (20 centile). The family history was significant for maternal family members with pregnancy losses of unknown etiology: one each for the mother and maternal grandmother. The great maternal grandmother reported at least 4 or 5 pregnancy losses. Consanguinity was denied. The proband remained in the neonatal intensive care unit for the next 8 months for management of severe respiratory issues, ascites and feeding difficulties. During that time, she underwent placement of a tracheostomy, a Denver (peritoneovenous) shunt for ascitic-fluid drainage, an intravenous port and a gastrostomy tube for feeds (Fig. 1). Additional pertinent findings then include retinopathy of prematurity, subglottal stenosis grade IV, hypothyroidism, 11 sets of ribs, mild bilateral hydronephrosis, accessory spleen and persistent ascites (Fig. 2). At 20 months dysmorphologic evaluation was significant for macrocephaly, open anterior and posterior fontanelles, bicoronal craniosynostosis on CT scan, right posterior plagiocephaly, brachycephaly, cupped and prominent ears with hypoplastic antihelices, broad forehead, a short and upturned nose, telecanthus, ocular hypertelorism, depressed nasal bridge (Figure 3A–B), moderate ascites, bilateral overriding of the second and fourth toes over the third toe, short stature and hypotonia. At this latter time, she exhibited significant developmental delays; she was unable to sit unassisted or feed herself. However, she was able to crawl, pull to a stand and sit independently. The proband could feed herself but still required a G-tube for much of her nutrition. She was nonverbal but able to use 12 signs. She continued to require a tracheostomy but only for night-time mechanical ventilation. At 33 months when last evaluated, her height was 79.2 cm (<1 centile), weight was 11.6 kg (7 centile) and OFC was 56 cm (>97 centile). The patient’s severe ascites persisted throughout the first 2 years of her life. At age 22 months, she underwent lymphatic imaging at the Children’s Hospital of Philadelphia that revealed multiple dilated perihepatic lymphatic vessels and leakage of contrast material into the peritoneum (Fig. 4A–D). Subsequently, she underwent successful embolization of these lymphatic vessels with resolution of her ascites.
先证者为一名混合白种人和日裔的 4 岁女性，经阴道自然分娩，孕期合并胎儿腹水、回声肠、羊水过多和宫颈机能不全。母亲无其他妊娠并发症，整个孕期未接触任何已知致畸物。她的身长为 37 厘米（第 37 百分位），体重为 1.478 千克（第 80 百分位），头围（OFC）为 27 厘米（第 20 百分位）。家族史中，母亲和外祖母都有不明原因的妊娠丢失：各一例。曾外祖母报告至少有 4 或 5 次妊娠丢失。否认近亲结婚。先证者因严重呼吸问题、腹水和喂养困难在新生儿重症监护病房接受治疗 8 个月。在此期间，她接受了气管造口术、丹佛（腹膜静脉）分流术以引流腹水、静脉港和胃造口管进行喂养（图 1）。其他相关发现包括早产儿视网膜病变、声门下狭窄 IV 级、甲状腺功能减退、11 对肋骨、双侧轻度肾积水、副脾和持续性腹水（图 2）。20 个月时的畸形学评估显示，头围大、前囟和后囟开放、CT 扫描显示矢状缝双侧早闭、右后部斜头畸形、短头畸形、杯状和突出的耳朵，耳轮发育不全、宽额头、短而上翘的鼻子、内眦赘皮、眼球突出、鼻梁凹陷（图 3A-B）、中度腹水、第二和第四脚趾超过第三脚趾重叠、身材矮小和张力减退。此时，她表现出明显的发育迟缓；她无法独自坐立或进食。然而，她能够爬行、拉站和独立坐。先证者能够自行进食，但仍需要 G 管来提供大部分营养。她无法言语，但能够使用 12 个手势。她仍需要气管造口术，但仅在夜间进行机械通气。最后一次评估时，她的身高为 79.2 厘米（低于第 1 百分位），体重为 11.6 千克（第 7 百分位），头围为 56 厘米（大于第 97 百分位）。患者的严重腹水持续存在于她生命的头 2 年。22 个月时，她在费城儿童医院进行了淋巴成像，显示多个肝周扩张的淋巴管和造影剂漏入腹膜（图 4A-D）。随后，她成功地对这些淋巴管进行了栓塞，腹水得到了缓解。
