The Beckwith–Wiedemann spectrum (BWSp) ranges from isolated lateralized overgrowth (ILO) to classic phenotypes. In this broad clinical spectrum, an epigenetic alteration on chromosome 11p15.5 can be detected. The risk for embryonal tumors is high, especially in patients with lateralized overgrowth (LO). The aim of this study is to investigate epigenetic alterations in 11p15.5 and tumor risk in 87 children with LO. The methylation level of 11p15.5 was examined in the blood of all patients and in skin samples or buccal swabs from 40 patients with negative blood tests; 63.2% of patients were compatible with the ILO phenotype, 18.4% were atypical, and 18.4% were classic. The molecular diagnosis rate was 81.2% for the atypical and classic phenotypes, and 10.9% for the ILO phenotype. In patients with epigenetic alterations, LO was statistically significantly more severe than in test negatives. Tumors developed in six (6.9%) of the total 87 patients with LO; four belonged to the atypical or classical phenotype (12.5%) and two to ILO (3.5%). Three of the four patients with atypical/classical phenotypes had pUPD11, one had IC1-GOM alteration, and two ILO patients were negative. We conclude that LO patients should be monitored for tumor risk even if their epigenetic tests are negative.

Objective:Williams syndrome is caused by a microdeletion at 7q11.23 and is characterized by a distinctive face, cardiovascular disease, and intellectual disability with a specific cognitive and behavioral profile. This study aims to evaluate the clinical features and obtain important information that can guide early diagnoses and correct follow-up. Materials and Methods: The study included 78 patients whose diagnoses were confirmed by fluorescent in situ hybridization. Facial features, anthropometric measurements, and neurocognitive, endocrine, and urinary system evaluations were obtained from the medical records, and photographs of the patients were evaluated retrospectively. Results: The most common complaints at admission were cardiovascular disease and atypical face. The mean age at admission was 39 ± 4.8 months. The mean age of patients presenting with atypical face was 41 ± 5.6 months, while it was 11 ± 3.1 months in patients presenting with cardiovascular disease. Short nose/bulbous nasal type with anteverted nares and periorbital fullness, which are diagnostic facial features, were present in all patients in the infantile/ early childhood period. 80% of the patients had cardiovascular disease; supravalvular aortic stenosis (53.8%) and peripheral pulmonary artery stenosis (41%) were the most common cardiac anomalies.Intel lectu al/de velop menta l disability was present in 75.6% of the patients. Behavioral disorders including autism spectrum disorder and attention deficit hyperactivity disorder were detected in 50% of our patients. Hypersensitivity to loud and/or sudden sounds was present in all patients. Conclusion: We highlighted that recognition of facial findings is important for early diagnosis, especially in patients without cardiovascular disease. The frequency of cardiovascular, endocrinological, renal anomalies, and intellectual disab ility /deve lopme ntal delay was described that provide valuable information in the follow-up of patients. Cite this article as: Bozlak S, Uludağ Alkaya D, Kasap B, et al. A large Turkish cohort of Williams syndrome: The evaluation of facial, cardiovascular, and neuropsychiatric features. Turk Arch Pediatr. 2023;58(2):182-188.

Objective: Joubert syndrome (JS) is a rare neurodevelopmental ciliopathy defined by the molar tooth sign (MTS) on brain magnetic resonance imaging accompanied by hypotonia, oculomotor apraxia (OMA), developmental delay, and multisystem involvement. With over 40 genes implicated, JS displays genetic and phenotypic heterogeneity. This study aimed to define the clinical and molecular spectrum of JS in a Turkish cohort. Materials and Methods: This study included 31 JS patients from 28 unrelated families, followed for 7.4 years. Genetic variants were identified using whole exome sequencing and confirmed by Sanger sequencing. Results: Genetic diagnosis was established in 23 families in 13 JS-related genes, with AHI1 (17.9%) and CEP290 (14.3%) most frequently affected. Thirteen novel variants were identified, including a variant of uncertain significance in NPHP4 in a patient with OMA, retinal involvement, MTS, and grade-III vesicoureteral reflux (VUR). The MTS was absent in 2 AHI1 and atypical in 1 TMEM107 patient; others exhibited typical MTS. Ptosis occurred in all MKS1 and TCTN2 patients. Retinopathy and vision impairment were most common in AHI1 and CEP290. Cognitive outcomes varied; normal cognitive function was seen in 1 AHI1 and 1 CEP290 case. Renal/hepatic involvement was generally mild; kidney hypoplasia occurred in 1 AHI1, VUR in 1 NPHP4, and transient transaminase elevation in 1 TCTN2 patient. One patient without a genetic diagnosis had situs inversus totalis. Intra-familial variability occurred among siblings carrying an AHI1 variant. Conclusion: This study highlights the genotypic and phenotypic diversity of JS, identifying 13 novel variants and suggesting NPHP4 as a potential JS-associated gene.

Background/Objectives: Severe neurodevelopmental disorders caused by homozygous ASTN1 variants have recently been reported. The aim of this study is to present the expanded phenotype and prognostic findings through a longitudinal follow-up of a patient with a homozygous ASTN1 variant. Methods: We conducted a 15-year clinical evaluation of a girl who initially presented at 10 years of age. The genetic etiology was investigated using exome sequencing. Results: The patient had a profound intellectual disability, severe expressive language delay, and infantile-onset epilepsy. She also had microcephaly, achieved independent walking at age 7 and had speech limited to only two words at admission. A novel homozygous frameshift variant, c.2096del (p.Cys699Serfs*22), in ASTN1 was identified. Over the follow-up period, her postnatal microcephaly became more pronounced, and she experienced a late relapse into generalized tonic–clonic seizures after a decade-long remission. She remains entirely dependent on caregivers for basic self-care at age 25. Conclusions: ASTN1-related phenotype is associated with a severe neurodevelopmental disease, and the late relapse of seizures after prolonged remission highlights the need for lifelong neurological monitoring and multidisciplinary care.