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.
ABSTRACT
OBJECTIVES: To investigate the presence of toxoplasmosis, rubella, cytomegalovirus, and herpes (TORCH) infections in women attending at the antenatal care clinic in Abha, Kingdom of Saudi Arabia (KSA). Methods: A total of 190 blood samples were collected from Abha maternity hospital in Aseer region, KSA, from February 2018 to May 2019 and screened with the TORCH panel (toxoplasmagondii [IgG/IgM], cytomegalovirus [CMV] [IgG/IgM], rubella [IgG/IgM], and herpes simplex type 1 and 2 [IgG/IgM]). RESULTS: The mean age was 31.42±6.514 years and gestational age was 32.48±6.168 weeks. Serum IgG was positive for Toxoplasma gondii (T. gondii) (27.4%), herpes simplex type 1 (HSV-1) (94.7%), herpes simplex type 2 (HSV-2) (0.5%), CMV (100%), and rubella (88.9%). Serum IgM was positive only for CMV (9.5%). Though, there was an association between abortions from previous pregnancies (26.5%), intrauterine death (5.8%), premature labor (3.2%), microcephaly (1.6%), other congenital diseases (1.6%) and low birth weight (0.5%) with current IgG positivity for TORCH infections, the results were not statistically significant. CONCLUSION: Seropositivity for IgG antibodies correlate with TORCH-associated pregnancy complications in Abha, KSA; however, IgM positive CMV pregnant cases warrant further systematic investigation to understand the implications of CMV on outcomes during pregnancy.
