PDF(Pubmed)
Abstract：
Jeune syndrome, or asphyxiating thoracic dystrophy (JATD), is a rare autosomal recessive skeletal dysplasia with heterogeneous genetic and clinical phenotypes, which primarily affects cartilage and bone development. Herein, we report a patient with a lethal form of SRTD3 without polydactyly (JATD), which led to severe restrictive lung disease and fatal respiratory failure. A full-term boy was born to a 30-year-old mother who was known to have hypothyroidism and was on thyroxine. The parents were first-degree cousins and had one healthy older son. Fetal ultrasound showed a cephalic fetus, normal amniotic fluid and a fundal placenta. All long bones and ribs were below the 1% percentile. The femur was bowed with no fractures or signs of significant demineralization at time of imaging. Head and abdominal circumference were within normal range. An echocardiogram on the 2nd day of life showed severe pulmonary hypertension (PHTN). Nitric oxide was started due to the presence of persistent hypoxia and severe PHTN. The patient continued to require high cardiorespiratory support, but the medical condition worsened, and respiratory failure persisted. The patient died of severe respiratory failure at 16 days of life due to respiratory insufficiency secondary to a severely restricted thoracic cage. Whole-exome sequencing (WES) revealed a homozygous mutation in the DYNC2H1 (NM_001377.3) gene, namely, the c.9041G>T NP_001368.2: p.(Arg3014Ile) missense variant, which results in the substitution of the arginine codon at amino acid position 3014 with an isoleucine codon. The phenotyping of the patient\'s JATD and the detection of a homozygous variant in the DYNC2H1 gene confirmed the diagnosis of short-rib thoracic dysplasia-3 without polydactyly. In summary, the patient had isolated skeletal anomalies without polydactyly or other organ involvement. Additionally, the infant had severe PHTN on top of the respiratory failure, which eventually caused death. Considerably more work will need to be done to determine the clinical spectrum of JATD and understand its genetic heterogeneity.
摘要：
Jeune综合征,或窒息性胸廓营养不良（JATD），是一种罕见的常染色体隐性遗传骨骼发育不良，具有异质性遗传和临床表型，主要影响软骨和骨骼发育。在这里，我们报告了一个患者的致命形式的SRTD3没有多指（JATD），导致严重的限制性肺病和致命的呼吸衰竭。一位30岁的母亲出生了一个足月男孩，该母亲患有甲状腺功能减退症，并且正在服用甲状腺素。父母是一级表亲，有一个健康的大儿子。胎儿超声显示头型胎儿,正常羊水和胎盘。所有长骨和肋骨均低于1%百分位数。股骨弯曲，在成像时没有骨折或明显脱矿的迹象。头围和腹围在正常范围内。生命第2天的超声心动图显示严重的肺动脉高压（PHTN）。一氧化氮是由于持续缺氧和严重的PHTN的存在而开始的。患者继续需要高心肺支持，但是医疗状况恶化了，呼吸衰竭持续存在。该患者在生命的16天死于严重的呼吸衰竭，原因是严重受限的胸廓继发的呼吸功能不全。全外显子组测序（WES）揭示了DYNC2H1（NM_001377.3）基因的纯合突变，即,c.9041G>TNP_001368.2:p.(Arg3014Ile)错义变体，这导致氨基酸位置3014处的精氨酸密码子被异亮氨酸密码子取代。患者JATD的表型和DYNC2H1基因纯合变异体的检测证实了短肋骨胸部发育不良-3的诊断，没有多指。总之,患者有孤立的骨骼异常，没有多指或其他器官受累。此外,婴儿在呼吸衰竭的顶部有严重的PHTN，最终导致死亡。需要做更多的工作来确定JATD的临床谱并了解其遗传异质性。
