Objective: The study aimed to show the clinical characteristics and prognosis of the L1 syndrome in patients with L1CAM mutations in the extracellular region. Materials and Methods: Three affected boys and their siblings and parents from a large family were included in this study. Genetic etiology was investigated by whole-exome sequencing in the index patient. The pathogenic variant was detected by whole-exome sequencing and was validated by Sanger sequencing in 3 patients and other family members. Results: We present 2 brothers and their cousin with prenatal onset hydrocephalus, severe developmental and speech delay, corpus callosum agenesis/hypogenesis, epilepsia, and adducted thumbs. A hemizygous missense mutation NM_024003 (c.A2351G:p.Y784C) on exon 18 of L1CAM gene was found in the 3 patients and their carrier mother. This missense mutation in the conserved region of the second fibronectin type III-like repeats located in the extracellular region of L1CAM resulted in the severe phenotype of X-linked inherited L1 syndrome in the patients. Conclusion: L1 syndrome should be considered in the differential diagnosis of male children with intellectual disability, hydrocephalus, and adducted thumbs. While truncating mutations of L1CAM may cause a more severe phenotype, missense mutations cause milder forms. However, pathogenic missense mutations affecting key amino acid residues lead to severe phenotype likely Cite this article as: Tüysüz B, Ercan-Şençiçek AG, Özer E, Goc N, Yalçınkaya C, Bilguvar K. Severe phenotype in patients with X-linked hydrocephalus caused by a missense mutation in L1CAM. Turk Arch Pediatr. 2022;57(5):521-525.

Loss of methylation (LoM) of the imprinting control region 1 (ICR1) in the chromosome 11p15.5 domain is detected in patients with Silver-Russell syndrome (SRS), characterized by asymmetric pre- and postnatal growth restriction, and typical craniofacial features. The patients with intrauterine growth restriction (IUGR) possess a high risk for adult metabolic problems. This study is aimed to investigate the methylation levels of the chromosome 11p15.5 region and metabolic problems in children with syndromic and nonsyndromic IUGR. Methylation analysis was performed for chromosome 11p15.5 in 49 patients (33 with suspected SRS and 16 nonsyndromic IUGR) with Netchine-Harbison clinical scoring (NHCS); uniparental disomy for chromosomes 6, 7, 14, and 20 was evaluated for those who were negative. LoM of ICR1 was detected in 14 of 33 suspected SRS patients with 3 or more criteria of NHCS, 5 had borderline LoM. Maternal uniparental disomy of the chromosomes 7 and 14 was found in 2 patients. The overall detection rate of SRS was 45.5%. While clinical findings were similar in patients with LoM and borderline LoM of ICR1, typical craniofacial findings were significantly less in the patients with normal methylation. Methylation patterns were not found to be impaired in the nonsyndromic IUGR group. Metabolic complications were evaluated in a total of 63 patients including 33 SRS-suspicious, 16 nonsyndromic IUGR, and 14 patients with 3M or SHORT syndrome. Increased rates of hypercalciuria, insulin resistance, and dyslipidemia were detected in patients with both syndromic and nonsyndromic IUGR. We would like to emphasize that detecting typical facial findings is effective in the diagnosis of SRS and paying attention to metabolic problems in the follow-up of patients with IUGR is recommended.

Background Menstrual irregularities are common among adolescents, often linked to anovulatory cycles. This study aims to establish diagnostic cut-off values for Polycystic Ovary Syndrome (PCOS) and differentiate these from anovulatory dysfunction in adolescents. Additionally, we assessed the sensitivity of using the Free Androgen Index (FAI) and Sex Hormone Binding Globulin (SHBG) in diagnosing PCOS. Methods This study included 305 adolescents presenting with oligomenorrhea at a tertiary center. Data were analyzed statistically and Receiver operating characteristic (ROC) curves were plotted to evaluate diagnostic performance. Results Of the 305 patients, 229 (75%) had anovulatory cycles and 36 (11.8%) had PCOS. The mean FAI values for anovulatory cycles, PCOS, and hyperinsulinism were 3.5 ± 2, 8.0 ± 5, and 8.3 ± 4, respectively (p < 0.001). A significant positive correlation was found between FAI and both HOMA-IR (r = 0.389; p < 0.001) and BMI (r = 0.499; p < 0.001). ROC analysis determined the LH threshold of 9.7 U/L and LH/FSH ratio threshold of 2.62 as predictive markers for PCOS. Conclusions Anovulatory cycles are the most frequent cause of menstrual irregularities in adolescents, with hyperandrogenism being crucial for diagnosing PCOS. The FAI may be unreliable for PCOS diagnosis due to similar values in adolescents with hyperinsulinemia and obesity. Lower SHBG levels in hyperinsulinemic obese adolescents further complicate the use of FAI, indicating that glucose/insulin metabolism significantly influences FAI/SHBG levels. Comprehensive diagnostic criteria, including androgen levels, LH/FSH ratio, SHBG, FAI levels, and ovarian ultrasound, are essential for accurate PCOS diagnosis.

Background/Objectives: To evaluate pancreatic size and echogenicity using ultrasonography in newly diagnosed pediatric Type 1 Diabetes Mellitus patients within five days of diagnosis, and compare early childhood (<7 years) and adolescent (≥13 years) endotypes with clinical and laboratory findings. Methods: This prospective, cross-sectional, case–control study included 69 pediatric patients with newly diagnosed type 1 diabetes mellitus, aged 1–18 years, and 78 age- and sex-matched healthy controls. Patients with chronic conditions (e.g., pancreatitis or cystic fibrosis), other forms of diabetes, or medications affecting glucose metabolism were excluded. Ultrasonography was performed within five days of diagnosis, after metabolic stabilization, to assess pancreatic dimensions and echogenicity. Laboratory analyses included measurements of C-peptide, HbA1c, and autoantibodies (anti-GAD, islet cell antibody, and insulin antibody). Results: Pancreatic dimensions were significantly smaller in type 1 diabetes mellitus patients (p < 0.001), with greater reductions in adolescents (head: 21%, body: 26.7%) vs. young children (head: 14.4%, body: 15.5%). Isoechoic pancreases were more common in young patients (80% vs. 40.9%; p = 0.033). C-peptide and HgbA1c were higher in adolescents (p < 0.05), with no echogenicity–autoantibody association. Conclusions: This first early-post-diagnosis ultrasonography study reveals age-specific pancreatic atrophy and echogenicity changes in children, more severe in adolescents, reflecting type 1 diabetes mellitus endotypes. Ultrasonography offers a practical noninvasive tool for early detection and endotype stratification, informing personalized diabetes care.

Objective: Small for gestational age (SGA) is a heterogeneous condition influenced by fetal, placental, maternal, and genetic factors. While most SGA children experience catch-up growth within the first two years, up to 10-15% remain short-statured and may require growth hormone (GH) therapy. This study evaluated the clinical characteristics, genetic factors, and responses to recombinant GH (rGH) therapy in non-syndromic SGA children with persistent short stature. Material and Methods: We retrospectively analyzed 36 non-syndromic short-statured children born SGA who were evaluated in a tertiary center. Genetic testing, including karyotyping and microarray analysis for copy number variations (CNVs), was performed. Growth response to rGH therapy was assessed in 19 patients over a three-year period. Results: Among the 19 patients receiving rGH therapy, the mean height SDS improved from -3.04±0.58 at baseline to -2.07±0.67 after three years, with an average gain of 0.97 SDS. CNVs were identified in 6 patients (16.66%), with several pathogenic or likely pathogenic variants, including deletions and duplications in regions associated with growth and developmental disorders. Conclusion: A significant proportion of non-syndromic SGA children with persistent short stature exhibit CNVs, underscoring the genetic complexity of this condition. rGH therapy effectively improves growth outcomes, but individual responses vary. These findings highlight the need for routine genetic screening and personalized treatment strategies to optimize care for SGA children.