Molecular Syndromology最新文献

[This corrects the article DOI: 10.1159/000545585.].

Introduction: Opsismodysplasia (OPS) is a rare skeletal dysplasia characterized by delayed bone maturation, distinctive skeletal deformities, and severe growth impairment. Mutations in the INPPL1 gene, particularly homozygous variants, are the primary genetic cause of this condition. While bisphosphonate therapy has shown efficacy in OPS cases with hypophosphatemic rickets, its role in cases without this complication remains unclear.

Case presentation: A 2-year-and-2-month-old girl with OPS was treated with intravenous pamidronate (0.5 mg/kg/3 months). Initial evaluations showed severe short stature and low bone mineral density (DEXA SDS: -3.16). After three courses of treatment, the patient achieved independent walking, and her DEXA SDS improved to -2.5 over 1 year.

Discussion: Pamidronate is effective in treating OPS even in the absence of hypophosphatemic rickets, showing potential as a therapeutic option for this rare condition.

Introduction: Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome is a rare multisystemic congenital disorder caused by SON gene variants. This study aimed to present the results of whole exome sequencing, and describe some rare findings observed in the proband.

Case presentation: An 11-year-old boy exhibited hypotonia, poor growth, short stature, and microcephaly. The patient displayed various neurological symptoms, such as developmental delay, seizures, hydrocephalus, and brain abnormalities. He presented with strabismus, urinary problems, and facial dysmorphism. A history of stroke, obsession, insomnia, self-injurious behavior, and hearing loss was also noted. Based on the patient's clinical findings, whole exome sequencing was performed. A novel variant in the SON gene was identified. This variant was confirmed by Sanger sequencing. Notably, the parents tested normal for the variant.

Conclusion: This study presents a patient who exhibited a wide range of behavioral abnormalities, stroke, and recurrent urolithiasis - features that are rarely reported in ZTTK syndrome - and includes a review of the literature.

Introduction: Turner syndrome is a complicated gonadal insufficiency, infertility, and endocrine disease caused by the partial to complete loss of one X chromosome. Women with Turner syndrome have been reported to show altered effector T-cell subgroups; however, the relationship between T-cell subgroups and chromosome type remains unknown.

Methods: In this study, we investigated immune abnormalities and karyotypes of Turner syndrome. Using flowcytometry, we examined the T-cell subsets of 20 women with Turner syndrome and 23 women serving as controls (without recurrent pregnancy loss), between July 2021 and June 2022. Background data of the women with Turner syndrome were also collected.

Results: Significantly lower levels of helper T-cells 1 and 2 were observed in women with Turner syndrome than in the control group (4.5 ± 2.88 vs. 8.54 ± 4.45, p < 0.05, 0.56 ± 0.38 vs. 0.97 ± 0.48, p < 0.05, respectively). With respect to karyotypes, deletion of a specific region, pseudoautosomal region 2, which typically escapes X-inactivation, might influence regulatory T cells (Treg) levels as copy number of PAR2 and Treg rate were positively correlated (r = 0.76).

Conclusion: Individuals with Turner syndrome showed an altered T-cell subset, which might be caused by the deletion of a specific part of the X chromosome, pseudoautosomal region 2. This finding suggests that women with Turner syndrome in a specific karyotype show altered T-cell subsets, and more cases are needed to determine whether these T-cell changes could influence pregnancy outcomes.

Introduction: X-linked intellectual disability (XLID) is a highly heterogeneous disease. Apart from Fragile X, other diseases that cause XLID are quite rare. The DLG3 gene variants cause XLID90.

Case presentation: This study presents 2 patients diagnosed with XLID90 after identifying a novel variant in the DLG3 gene through whole exome sequencing analysis. Both patients had autism spectrum disorder, intellectual disability, and dysmorphism. Additionally, an arachnoid cyst, which has not been previously reported in XLID90, was also detected in the patients. XLID90 has neither specific clinical findings nor dysmorphic features. Therefore, a detailed literature review is essential for clearly elucidating the phenotype. Here, one hundred and two XLID90 cases from 18 publications reporting pathogenic variants in the DLG3 gene were reviewed to investigate the detailed clinical findings among these patients. The literature review has shown that ID is more frequently observed in patients with truncating variants, while seizures are more commonly seen in patients with non-truncating variants.

Conclusion: This study will provide homogeneous healthcare to patients and allow for appropriate genetic counseling.

[This corrects the article DOI: 10.1159/000543315.].

Introduction: Weiss-Kruszka syndrome is a rare, autosomal dominant neurodevelopmental disorder caused by pathogenic variants in the ZNF462, located at chromosome 9p31.2. Clinically, it is characterized by craniofacial dysmorphism, global developmental delay, intellectual disability, short stature, congenital anomalies of the heart and brain, and feeding difficulties. The phenotypic spectrum is notably heterogeneous, with variable expressivity and occasional incomplete penetrance.

Case presentation: Herein, we report a novel de novo heterozygous frameshift variant in ZNF462, designated c.2924del; p.(Gln975ArgfsTer3) (NM_021224.6), identified in a pediatric patient.

Conclusion: Importantly, our patient presented with a congenital diaphragmatic hernia - an anomaly not previously described in association with Weiss-Kruszka syndrome. To date, 48 cases have been reported in the literature. Our findings further broaden the phenotypic spectrum linked to ZNF462 variants and emphasize the need for continued clinical and molecular characterization. Through the detailed documentation of this unique case, we aimed to enhance the understanding of the clinical variability and potential comorbidities associated with this emerging syndrome.

Introduction: Rubinstein-Taybi syndrome (RSTS) is characterized by distinctive craniofacial features, growth deficiencies, and broad thumbs and halluces. Most diagnoses are made through sequence analysis of the CREBBP or EP300 genes. Here we focused on two cases diagnosed through chromosomal microarray analysis (CMA), highlighting the significance of genetic variations in RSTS.

Case presentation: After detailed clinical examinations and genetic evaluations of 2 patients with suspected RSTS, CMA was conducted to identify copy number variations. CMA revealed a 128-kb deletion in the CREBBP gene in case 1 presenting with dysmorphic features and growth delays. Case 2, a 14-month-old girl with global developmental delay and similar dysmorphic features, was found to have a 1,467-kb deletion encompassing part of the EP300 gene.

Conclusion: Our study underscores the importance of CMA as a critical diagnostic tool for RSTS, particularly in cases where sequence analysis fails to identify pathogenic variants. The identification of significant deletions in the CREBBP and EP300 genes through CMA not only confirms the diagnosis of RSTS but also expands our understanding of the genetic complexity of the syndrome. Since CMA is already included as part of the diagnostic evaluation for RSTS, these findings further emphasize its value in ensuring accurate diagnosis and improving the management of this rare condition.

Introduction: Kniest dysplasia is a rare skeletal disorder, characterized by mild dysmorphic features, cleft palate, short stature, short limbs, prominent joints, restricted joint mobility, hearing impairment, and ocular manifestations such as high-degree myopia, retinal detachment, and cataract. Typical radiological findings include platyspondyly, coronal clefts, and dumbbell-shaped long tubular bones.

Case presentation: Herein, we report on an 8-month-old boy who was referred to the pediatric genetic department due to narrow thorax and short extremities. He had mild dysmorphic features, cleft palate, narrow thorax, short extremities, and short stature. On radiographies, platyspondyly, hemivertebra, and dumbbell-shaped long tubular bones were detected. Clinical and radiological findings were consistent with Kniest dysplasia. Clinical exome sequencing was performed and revealed a heterozygous, pathogenic c.905C>T (p.Ala302Val) variant in the COL2A1 gene, confirming the initial clinical diagnosis.

Discussion: Kniest dysplasia is a very rare skeletal dysplasia, and an accurate clinical diagnosis is important to provide the best possible follow-up.

Introduction: Shashi-Pena syndrome (SHAPNS) is a rare congenital disorder characterized by macrocephaly, delayed psychomotor development with intellectual disability, hypotonia, seizures, episodic hypoglycemia, distinct facial features, and glabellar nevus flammeus, caused by heterozygous variants of the ASXL2 gene.

Case presentation: We report on a 15-year-old patient in care at our hospital since the age of 4 years presenting with minor neurodevelopmental problems, marked postnatal overgrowth without advanced bone age, and dental anomalies.

Conclusion: Patients described in the literature with SHAPNS are reported indicating a broad spectrum of clinical manifestations. The present patient manifests an atypical presentation of SHAPNS due to a novel heterozygous ASXL2 variant. This study supports the inclusion of SHAPNS in overgrowth disorders with macrocephaly, suggesting the analysis of the ASXL2 gene even in suspected subjects with normal bone age and confirms dental anomalies as a clinical feature of this syndrome. SHAPNS could be inferred even in the absence of developmental delay or epilepsy.