Case Reports in Genetics最新文献

Introduction: Emanuel syndrome is a rare chromosomal disorder characterized by severe developmental disability and variable clinical manifestations. Although congenital anomalies are relatively common, there is no pathognomonic prenatal pattern. In some cases, structural defects are absent or not detectable prenatally, making the potential role of soft ultrasound markers particularly relevant.

Case presentation: We report a case of Emanuel syndrome in which no structural malformations were identified prenatally. First-trimester ultrasound revealed an isolated increased nuchal translucency of 3.2 mm. Postnatally, the infant exhibited severe hypotonia, dysmorphic features, and profound developmental delay, but no gross structural defects were observed. Cytogenetic and FISH analyses confirmed an additional der(22)t(11; 22) chromosome inherited from the mother.

Discussion: A review of the limited literature on first-trimester findings suggests that increased nuchal translucency has been observed in several cases of Emanuel syndrome, although the available data remain insufficient to assess predictive value. Nevertheless, the recurrence of this observation across independent reports indicates that NT enlargement may warrant attention as a potential prenatal marker.

Conclusion: While current evidence is insufficient to draw definitive conclusions, this case highlights that isolated NT thickening may represent the only prenatal sign of Emanuel syndrome. Evaluation in larger cohorts and future prospective studies will be essential to determine the sensitivity and specificity of this marker for early diagnosis of the syndrome and the timely identification of balanced translocation carriers.

Sickle cell trait (SCT) increases the risk of sudden death and exertional rhabdomyolysis (ER) in athletes and Service Members (SMs) during intense exercise. Exertional injuries in SCT carriers can result in exercise collapse associated with SCT (ECAST), an under-recognized condition characterized by variable clinical presentations ranging from ischemic muscle pain to fulminant collapse. This study presents clinical and genetic findings of two independent Black SMs with history of ECAST triggered by strenuous exercise. ECAST cases carried pathogenic heterozygous mutations POLG: p.Gly848Ser and RRM2B: p.Met282Ile associated with mitochondrial DNA depletion syndromes. Mononuclear cell mitochondria extracted from ECAST cases showed impaired mitochondrial profiles and resilience, demonstrating the potential contribution of mitochondrial dysfunction to exertional collapse in SCT carriers.

Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-related overgrowth spectrum (PROS) is a group of rare genetic asymmetric and atypical overgrowth disorder syndromes. Affecting skin, adipose and connective tissues, brain, bone, and vasculature and severity influenced by the gestational age at which the change occurred, PROS is phenotypically heterogeneous. This paper shares the case report of a former extremely preterm infant diagnosed with a subtype of PROS, megalencephaly-capillary malformation/megalencephaly-capillary malformation polymicrogyria (MCAP) syndrome, for whom treatment with alpelisib was initiated at 10 months of age (7 months corrected age). To our knowledge, this patient is the third and youngest to be included in this expanded access program for compassionate use for patients under 2 years of age.

Nonimmune hydrops fetalis (NIHF) refers to the pathologic accumulation of fluid within the fetus due to causes other than red cell alloimmunization and now accounts for up to 90% of fetal hydrops cases. Fetal hydrops is associated with significant morbidity and mortality, and the exact prognosis is largely dependent on the underlying etiology. The most common etiologies include cardiovascular causes and chromosomal or genetic abnormalities. Despite this, diagnostic testing with karyotype or chromosomal microarray only identifies approximately 25% of cases, and up to 20% of cases remain idiopathic or unknown. We report the first known case of NIHF related to a NOTCH1 pathogenic variant. In this case, NIHF was diagnosed at 30 weeks' gestation in a fetus with low-risk prenatal genetic screening, noncontributory anatomic survey, and normal chromosomal microarray. The hydrops was uniquely localized to scalp edema and pleural effusions requiring bilateral thoracentesis and never progressed to involve pericardial effusion or ascites. Whole exome sequencing diagnosed a novel pathogenic variant in the NOTCH1 gene. This is the first reported case of NIHF in the setting of NOTCH1 pathogenic variant and is an important addition to the existing literature on this incredibly diverse, high-risk pathology.

CDKN2A is the primary high-risk predisposition gene for familial cutaneous melanoma. In the Netherlands, most carriers of pathogenic germline variants in CDKN2A harbor a unique, population-specific founder variant, c.225_243del, commonly referred to as p16-Leiden. For decades, this distinctive 19 base-pair deletion in CDKN2A had been identified exclusively as a germline variant. Here, we report an exceptional case of somatic mosaicism for the p16-Leiden variant in an Irish male with a concurrent diagnosis of Kartagener's syndrome but no history of malignancy. The variant was first identified through targeted next-generation sequencing (NGS) of a fundic gland polyp in the distal esophagus, showing a variant allele frequency (VAF) of 40%. Subsequent analysis also detected the variant in the patient's buccal swab DNA (VAF 0.3%), while it was notably absent in multiple other tissue samples, including blood, urine, skin, and several additional samples from the proximal gastrointestinal tract. We explore several hypotheses that could explain these intriguing findings.

Uniparental disomy (UPD), the inheritance of two copies of a chromosome from one parent, can lead to recessive genetic disorders or imprinting effects. We report a case of autosomal recessive glycogen storage disease type 4 (GSD IV) due to maternal UPD of chromosome 3, representing the first reported instance of UPD leading to this rare disorder. To avoid an unjustified claim of misattributed paternity, the possibility of UPD should always be kept in mind in cases with the unique finding of the homozygous pathogenic variant only present in one parent. This case highlights the critical role of genetic counseling in uncovering rare genetic conditions and emphasizes the need for continued awareness of UPD in clinical genetics.

Deletions within the chromosomal locus 1p31.1 are rare, with only a limited number of documented cases. The typical clinical presentation includes intellectual disability, failure to thrive, and craniofacial abnormalities. Some cases may also present with cardiac, gastrointestinal, and genitourinary malformations. Variability in deletion size contributes to a broad spectrum of clinical phenotypes, and a comprehensive understanding of the syndrome's manifestations is still evolving. This case study aims to provide additional insights into 1p31.1 microdeletion syndrome, enhancing knowledge of its genetic and phenotypic characteristics to improve recognition by clinicians. Here, we report a case featuring a 14.385 Mb deletion isolated to the 1p31.1 region, encompassing 41 genes. The deletion manifested with microcephaly, distinctive facial morphology, hypotonia, developmental delay, bilateral cryptorchidism, and flat feet. Notably, our case also exhibited congenital thickening of the lingual and labial frenulum, a trait not typically associated with this deletion.

[This corrects the article DOI: 10.1155/2024/8099373.].

Uniparental disomy (UPD) constitutes an unconventional mode of inheritance that disrupts the typical biparental genetic contribution and may result in phenotypic abnormalities. This report centers on a patient diagnosed with Bartter syndrome Type 1, attributed to a homozygous pathogenic variant in SLC12A1 unmasked by mosaic paternal UPD of chromosome 15. We hypothesize that this pattern (or constellation) emerged from a trisomy rescue event, resulting in two distinct cell lines. Concurrently, the unmasking of a pathogenic paternal SLC12A1 variant by trisomy rescue resulted in the manifestation of Bartter syndrome Type 1. The maternally derived ring chromosome 15 and its impact on nondisjunction and UPD elucidate a unique etiology of Bartter syndrome. Furthermore, the presence of a pathogenic paternal SLC12A1 variant underscores the pivotal role of trisomic rescue and paternal UPD in unveiling a recessive variant.

Neonatal liver disease is a broad entity. When it presents in conjunction with other abnormalities, it raises the question of a potential underlying genetic cause. Etiologies that were once difficult to diagnose are becoming more readily identifiable with the arrival of next-generation sequencing. We present a rare cause of neonatal liver disease, a FOCAD gene variant, that was determined to be the most likely cause of an infant's liver disease and other findings. This case adds to only a few reports in the literature on this presentation in the neonatal period.