Peters-Plus syndrome is a rare autosomal recessive disorder caused by biallelic pathogenic variants in the B3GLCT gene and characterized by multisystem involvement. Fewer than 100 cases have been reported to date, and only a limited number have been diagnosed prenatally. Prenatal identification is challenging due to the variable and non-specific nature of fetal findings and the frequent absence of detectable ocular anomalies during routine ultrasound. We report a prenatal diagnosis of Peters-Plus syndrome in a monochorionic diamniotic twin pregnancy, based on the progressive identification of early-onset intrauterine growth restriction, rhizomelic limb shortening, craniofacial dysmorphism, and mild central nervous system abnormalities. Standard cytogenetic and chromosomal microarray analyses were normal, prompting extended genetic testing. Prenatal exome sequencing identified a homozygous pathogenic splice-site variant (c.660+1G>A) in B3GLCT in both fetuses, confirming the diagnosis. This case highlights the importance of recognizing suggestive multisystem prenatal findings and the crucial role of advanced genetic testing in achieving an accurate prenatal diagnosis. Early molecular confirmation enables appropriate parental counseling regarding prognosis, recurrence risk, and future reproductive options.

While low birth weight (LBW) is a recognized risk factor for adult metabolic syndrome, the unique lipid metabolic phenotype of late preterm low birth weight (LPTB-LBW) neonates-who experience dual exposures to shortened gestation and intrauterine growth restriction-remains uncharacterized. This study specifically examines whether the convergence of prematurity and growth restriction synergistically disrupts lipid metabolic programming. Using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), we compared lipidomic profiles of 88 plasma samples: 45 LPTB-LBW (340/7-366/7 weeks, <2,500 g) and 43 later preterm birth-normal birth weight (LPTB-NBW, 340/7-366/7 weeks, 2,500-4,000 g) controls. Multivariate orthogonal partial least squares-discriminant analysis and univariate modeling identified discriminant lipids. Maternal-neonatal lipid continuity was assessed through Spearman's correlation analysis. A total of 1,173 lipids were identified, categorized into five major lipid classes, with 349 significantly different lipids detected (324 upregulated and 25 downregulated) in the LPTB-LBW group. All glycerolipids were upregulated, accounting for 50% (162/324) of the upregulated lipids. Long-chain polyunsaturated triglycerides (TG) showed extreme elevations, such as TG (18:2_18:3_18:4) and TG (18:2_20:4_20:5). Monoglycerides, including MG (18:2) and MG (18:1), were also significantly elevated. Among glycerophospholipids (GP), 76 species were upregulated, with notable increases in phosphatidylethanolamines such as PE (O-18:0_22:3) and PE (18:2_22:1), while PG (20:4_22:6) was significantly reduced. All differentially expressed ceramides, including Cer (d26:3/33:1(2OH)), Cer (d29:2/30:2(2OH)), and Cer (d28:3/31:1(2OH)), were upregulated, whereas sphingosines were downregulated. Cholesterol esters were decreased, while bile acids, free fatty acids and acylcarnitines were elevated. KEGG pathway enrichment analysis highlighted significant perturbations in cholesterol, glycerolipid, and sphingolipid metabolism. Maternal high-density lipoprotein cholesterol (HDLC) levels during early pregnancy showed exclusive negative correlations with neonatal lipids, particularly triacylglycerol TG (16:0_18:2_18:2) (r =  - 0.33, p = 0.002), diacylglycerols, and ceramides, whereas no associations were observed for maternal low density lipoprotein (LDLC), TC, or TG. LPTB-LBW neonates exhibit a unique lipidomic phenotype marked by hyperaccumulation of glycerolipids (e.g., long-chain polyunsaturated TGs), elevated ceramides, and altered phospholipid species (increased PE, decreased PG). Maternal HDLC levels negatively correlated with specific neonatal lipids. These findings highlight early-life lipid alterations in LPTB-LBW infants and the need for further investigation into their clinical implications.

Dyskeratosis congenita (DC) is a rare multisystem disorder primarily characterized by bone marrow failure due to telomere shortening. Typical clinical features include oral leukoplakia, skin hyperpigmentation, and nail dystrophy, along with an increased risk of malignancies. Hoyeraal-Hreidarsson syndrome (HH), a severe variant of DC, is associated with profound neurological and immunological complications, emphasizing the importance of early diagnosis and genetic evaluation to guide appropriate management. The authors present a case of a 2-year-old girl diagnosed with Hoyeraal-Hreidarsson syndrome, linked to a newly discovered mutation in the poly (A)-specific ribonuclease (PARN) gene. The patient exhibited intrauterine growth retardation (IUGR), congenital cytomegalovirus (CMV) infection, immunodeficiency, microcephaly, and cerebellar hypoplasia. Whole-exome sequencing (WES) identified a novel mutation in the PARN gene. Hoyeraal-Hreidarsson syndrome, a severe form of DC, manifests with multisystem involvement and is genetically heterogeneous. Early genetic testing through techniques such as WES can aid in diagnosing rare syndromes like HH and guide treatment strategies, including bone marrow transplantation. This case underscores the importance of genetic evaluation in complex, rare syndromes like HH. Whole-exome sequencing plays a crucial role in identifying pathogenic mutations and tailoring management. The patient's prognosis is being closely monitored following bone marrow transplantation.

Analyze the ultrasound findings, single nucleotide polymorphism array (SNP-array) results, and pregnancy outcomes of fetuses with 7q11.23 deletions and duplications in the second and third trimesters. Investigate the prenatal ultrasound characteristics and follow up information of these fetuses. Seven fetuses were diagnosed with 7q11.23 deletion and six with 7q11.23 duplication via SNP-array at the prenatal diagnosis center of a single Chinese tertiary medical center from January 2017 to May 2024. Maternal demographics, ultrasound findings, SNP-array results, pregnancy outcomes, and follow-up information were comprehensively reviewed and analyzed. The copy number variations (CNVs) ranged from 1.43 Mb to 1.78 Mb in cases of 7q11.23 deletions and from 1.42 Mb to 1.68 Mb in cases of 7q11.23 duplications. These CNVs encompassed 29 OMIM-listed genes, including ELN, DNAJC30, GTF2IRD1, and GTF2I. Among the seven cases of 7q11.23 deletion syndrome, six exhibited ultrasound abnormalities. The main clinical phenotypes included three cases of intrauterine growth restriction and four cases of cardiovascular system abnormalities, specifically two cases with ventricular septal defects, one case with aortic narrowing, and one case with supravalvular pulmonary stenosis. One case was particularly notable, exhibiting complex multi-organ structural malformations. Out of six cases of 7q11.23 duplication syndrome, five exhibited ultrasound abnormalities. These included two cases of cardiovascular abnormalities: one case with a widened left ventricle and another case with a shortened fetal humerus length. One case revealed complex multi-organ structural malformations, including hydronephrosis, a microgallbladder, and a cleft lip and palate. All seven cases of 7q11.23 deletions and three cases of 7q11.23 duplications opted for termination of the pregnancy. The remaining three cases of 7q11.23 duplications chose to continue the pregnancy. One case underwent surgical treatment for a ventricular septal defect after birth, and the prognosis was favorable. Another case involved a full-term delivery, this child was followed up at the age of 4 and exhibited a phenotype of poor language expression ability. Our study broadened the clinical phenotype spectrum of fetuses with 7q11.23 deletions and duplications. Additionally, it conducted a preliminary evaluation of prenatal ultrasound findings and postnatal clinical phenotypes in follow-up cases. The clinical phenotype of fetuses with 7q11.23 deletion and duplication syndromes involves multiple systems and is relatively complex. Cardiovascular abnormalities and intrauterine growth restriction are the most common clinical manifestations observed in prenatal 7q11.23 deletion syndrome. Fetuses with 7q11.23 duplications exhibit a wide range of clinical phenotypes that lack specificity.

Congenital cataract is one of the most genetically heterogeneous ocular conditions with different genes involved in its etiology. Here, we describe the analysis of a new candidate gene of a congenital bilateral cataract associated with polymalformative syndrome, moderate global developmental delay, microcephaly, axial hypotonia, intrauterine growth restriction and facial dysmorphism for two affected siblings. Molecular analysis included exome sequencing and genome wide homozygosity mapping revealed a region of homozygosity shared by the two affected siblings at 10q11.23. The new C10orf71 gene was included in this interval and direct sequencing of this gene revealed an already described homozygous c. 2123T > G mutation (p. L708R) for the two affected subjects. Interestingly, we revealed in contrast a 4-bp deletion on the 3'-splicing acceptor site of intron 3-exon 4, namely defined as IVS3-5delGCAA. The C10Orf71 gene expression analysis using RT-PCR showed an expression pattern in different fetal organs and tissues as well as in leukocytes and confirmed that the IVS3-5delGCAA deletion of the C10orf71 gene is a splicing mutation responsible for the shortening of the C10orf71 protein in the two related patients. The C10orf71 gene has not been described to date as associated to the autosomal recessive phenotype.