Renal ciliopathies are a genetically and phenotypically heterogeneous group of diseases characterized by cystic and dysplastic kidneys. The aim of this study was to investigate the correlation between genetic changes that cause renal ciliopathies and phenotypic outcomes. The study group consisted of 137 patients diagnosed with renal ciliopathy disease. One hundred nineteen patients had ADPKD phenotype, 7 patients had ARPKD phenotype, 4 patients had nephronophthisis, 1 patient had Senior-Loken syndrome, 4 patients had Bardet-Biedl syndrome, 1 patient had Joubert syndrome and 1 patient had Meckel Gruber syndrome phenotype. Among patients with autosomal dominant polycystic kidney disease, patients with the PKD1 gene mutation had higher creatinine levels (p value: 0.020) and no arachnoid cysts were revealed in the PKD2 group (p value: 0.014). When the domains were compared, the finding of arachnoid cyst in patients with mutations in the transmembrane domain was statistically significant (p value: 0.021). Homozygous likely pathogenic variant in the TCTN1 gene was reported in a fetus who had findings of Meckel-Gruber syndrome; microphthalmia and cardiac hypoplasia were reported as novel findings. As a conclusion, we identified variant spectrum of renal ciliopathies in Turkish cohort and revealed the association between the transmembrane domain and arachnoid cyst.

Meckel-Gruber syndrome (MKS, OMIM 24,900), also known as Meckel syndrome, is a rare and severe autosomal recessive disorder. The syndrome is typically characterized by a triad of occipital encephalocele, bilateral renal cystic dysplasia, and postaxial polydactyly. MKS shows significant clinical heterogeneity, which poses challenges for accurate prenatal diagnosis. Prenatal ultrasound is an important tool for detecting potential cases, but the complexity of MKS often requires additional advanced techniques such as prenatal whole-exome sequencing (WES) to provide more accurate molecular genetic evidence. In this study, we used whole-exome sequencing (WES) to analyze the genetic causes of suspected MKS in a Chinese fetus. Sanger sequencing was used to confirm the origin of the variants. The classification of variants was carried out in accordance with the guidelines of the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP). A 26-year-old pregnant woman was referred to our antenatal centre for genetic diagnosis at 13 + 5 weeks of gestation due to fetal occipital encephalocele and renal cysts detected by ultrasound. Two novel heterozygous variants, c.1047delA (p.Val351fs*1) and c.1336C>T (p.Arg446*), were identified in TCTN2. Sanger sequencing revealed that the c.1047delA (p.Val351fs*1) variant was inherited from the mother and the c.1336C>T (p.Arg446*) variant was inherited from the father. According to the ACMG/AMP guidelines, these two variants were evaluated as pathogenic. This study further expands the genetic mutation spectrum of TCTN2 and is conducive to further clarifying the relationship between the genotype and phenotype of MKS8. Severe variants in the TCTN2 gene appear to be more likely to lead to MKS8. Clinically, the triad is an important basis for the diagnosis of MKS8, while other variable phenotypes of MKS8 can provide additional information for prenatal diagnosis. The combination of prenatal ultrasound and WES can provide a more comprehensive and accurate diagnosis of MKS8, which will greatly aid support for early intervention and treatment.

Senior-Løken syndrome is a rare autosomal recessive ciliopathy characterized by nephronophthisis and early-onset retinal dystrophy. It is typically diagnosed in childhood, and adult-onset diagnosis is rare and may delay renal-protective interventions. Here, we report a rare case of Senior-Løken syndrome in an adult with an IQCB1/NPHP5 mutation. A 20-year-old Turkish male presented with rotatory nystagmus since birth, progressive visual impairment from childhood, and chronic kidney disease that began during adolescence. The patient exhibited polyuria and polydipsia, and the ocular electrophysiology results were consistent with retinitis pigmentosa. Initial laboratory results were as follows: hemoglobin 11.03 g/dL, urea 56.65 mg/dL, creatinine 2.59 mg/dL, estimated glomerular filtration rate 34.14 mL/min/1.73 m2. Renal ultrasonography revealed increased parenchymal echogenicity, and abdominal computed tomography revealed small cystic lesions in both kidneys. Kidney biopsy revealed predominantly tubulointerstitial changes (tubular atrophy, basal membrane thickening, and interstitial fibrosis), and immunostaining was negative. Whole-exome sequencing identified homozygous full-gene deletion of IQCB1/NPHP5, confirming the diagnosis of SLS. The patient was managed with conservative and supportive treatments. Chronic kidney disease in Senior-Løken syndrome is often diagnosed late, leading to a poor clinical outcome. Early diagnosis and timely management of renal complications can prevent the progression to end-stage renal disease.

Persistent left superior vena cava is the most common thoracic venous anomaly. It is usually asymptomatic and discovered incidentally during diagnostic or therapeutic interventions. It can complicate central line insertion, causing arrythmias and thromboembolic complications. Joubert syndrome and related disorders are a group of rare congenital disorders associated with developmental abnormalities and multiple organ system involvement including renal, hepatic, and neurological manifestations. We report a case of a 12-year-old Kuwaiti Arab male child with Joubert syndrome, who was diagnosed with renal and hepatic failure and required central line insertion to initiate total parenteral nutrition. The central line was inserted through the left internal jugular vein because the patient had a dialysis catheter inserted in the right subclavian vein. After the line insertion, a chest X-ray revealed that the catheter appeared to descend directly into the left mediastinum rather than crossing to the right mediastinum through the innominate vein. Blood gas sample and subsequent echocardiography confirmed the presence of the catheter in a persistent left superior vena cava. The catheter was kept in place and used without complication for total parenteral nutrition and resuscitation for 18 days. Although persistent left superior vena cava is a rare anomaly, knowledge of its presence is important for the clinician in order to avoid complications associated with utilizing it for venous access, and to avoid unnecessary replacement for an uncomplicated catheter inserted in it. This is especially important for patients who would be expected to require invasive interventions, such as patients with Joubert syndrome.

Mutations of the OFD1 gene cause oral-facial-digital syndrome type 1 (OFD 1) and variations of the related ciliopathies Joubert syndrome and primary ciliary dyskinesia. OFD 1 manifests with skeletal, CNS, and renal abnormalities with prevalence estimated between 1 in 50,000 and 1 in 250,000. Cilia help regulate responses to mechanical forces in the renal tubules, and polycystic kidney disease (PKD) resulting from defective cilia is the primary determinant of morbidity in OFD 1. PKD associated with OFD 1 is rare before adulthood but may increase markedly with age, progressing to end-stage renal disease (ESRD) in 80% of cases. We report an 18-year-old female with congenital ciliopathy presenting with declining renal function and an increase of serum creatinine to 1.7 mg/dL. A 24-h urine collection yielded 0.8 g of creatinine and 500 mg of total protein. Imaging was conducted and genetic studies were repeated as her early childhood results were not available. MRI revealed numerous bilateral renal cysts consistent with progression of ciliopathy-associated PKD. Genetic testing confirmed the presence of a novel c.1332del frameshift mutation in the OFD1 gene, prematurely truncating the OFD1 protein. Modifications to diet and hydration to preserve renal function and delay progression to ESRD were initiated. This case of unusually early renal decline highlights the challenge of treating OFD 1. There are no currently approved medications and management consists of supportive measures to delay progression. Further research to better characterize and identify treatments for OFD 1 and related ciliopathies is warranted.