Pelin Özlem Şimşek Kiper

Biallelic pathogenic variants in UBR7 , encoding ubiquitin protein ligase E3 component n‐recognin 7, cause Li–Campeau syndrome (LICAS; OMIM #619189), which is characterized by developmental delay/intellectual disability, epilepsy, hypothyroidism, ptosis, genital anomalies, and cardiac anomalies. LICAS is an ultrarare disorder, and to date, only nine patients from eight unrelated families have been reported with detailed clinical phenotypes. Here, we report an 18‐year‐old female patient with dysmorphic facial features, ptosis, congenital hypothyroidism, intellectual disability, stereotypic hand movements, attention‐deficit/hyperactivity disorder, hepatosplenomegaly, and toenail hypoplasia. In contrast to previously reported patients, all of whom presented with global developmental delay, our patient achieved age‐appropriate early motor and language milestones, representing the mildest early developmental course reported in LICAS to date. Exome sequencing revealed a homozygous deletion encompassing Exon 7 of UBR7 , representing the first single‐exon deletion reported in this gene. This report expands both the phenotypic and genotypic spectrum of LICAS and underscores the clinical utility of Next generation sequencing‐based copy‐number variant analysis in the diagnostic workup of rare diseases.

Objective: 1p36 deletion syndrome is one of the most common contiguous gene deletion syndromes and is primarily characterized by a typical facial gestalt, as well as neurological problems and multisystemic involvement. This study presents the clinical findings of 17 patients with 1p36 deletion syndrome followed at a single center. Methods: Data from patients diagnosed with 1p36 deletion syndrome between 2010 and 2026 were retrospectively reviewed. Demographic characteristics, growth parameters, dysmorphic features, and neurological, cardiac, endocrine, visual, and auditory findings were analyzed, and the diagnostic methods used were evaluated. Results: A total of 17 patients (13 females and 4 males) were included in the study. Four patients were diagnosed using microarray analysis, and 13 using fluorescence in situ hybridization (FISH). Neurodevelopmental delay was observed in all patients. Typical facial gestalt was observed in the patients, with the most common dysmorphic facial features being straight eyebrows, deep-set eyes, and ear abnormalities. Central nervous system malformations were common, and epilepsy was observed in 70% of patients. Cardiac findings, ocular problems, hearing impairments, and hypothyroidism were also frequently identified. Three patients died, all due to respiratory failure. Conclusion: 1p36 deletion syndrome is a clinically recognizable condition, and early diagnosis and referral for appropriate management are important for improving prognosis. Although phenotypes associated with variable deletion sizes and genes located within critical regions have been reported, a multisystem approach is required in this syndrome due to its variable clinical presentation.

Background. Stuve–Wiedemann syndrome is a rare autosomal recessive bent-bone dysplasia characterized by dysautonomia and distinctive skeletal abnormalities, most commonly caused by biallelic LIFR variants. Methods. Eleven patients from ten unrelated families with molecularly confirmed Stuve–Wiedemann syndrome were evaluated. Detailed demographic, perinatal, clinical, radiographic, and molecular data were collected. All patients underwent Sanger sequencing of LIFR. Results. Respiratory problems and episodic hyperthermia were present in all patients, while feeding difficulties, hypotonia, growth failure, developmental delay, craniofacial dysmorphism, oral abnormalities, and ocular involvement were also common. All patients demonstrated long-bone bowing, cortical thickening, and flared metaphyses. A biallelic LIFR variant was identified in all patients, occurring in the homozygous state in nine patients and in the compound heterozygous state in two patients. The recurrent c.2074C>T; p.(Arg692Ter) variant was homozygous in seven patients and compound heterozygous in one patient. Three novel LIFR variants were also identified. Conclusion. Stuve–Wiedemann syndrome is characterized by a high mortality rate during the first two years of life due to severe dysautonomia, and orthopedic complications worsen progressively with age; therefore, early diagnosis and lifelong multidisciplinary follow-up are essential. Furthermore, the high rate of consanguinity in Türkiye, together with the recurrent p.(Arg692Ter) variant in LIFR identified in multiple unrelated families, supports the possibility of a founder effect and suggests that the frequency of Stuve–Wiedemann syndrome in our population may be higher than expected. Our findings further characterize the previously reported clinical manifestations of Stuve–Wiedemann syndrome while expanding the molecular spectrum through the identification of three novel LIFR variants.

Menke-Hennekam syndrome types 1 and 2 (MKHK1 and MKHK2) are autosomal dominant neurodevelopmental disorders characterized by psychomotor developmental delay, intellectual disability, and dysmorphic features. MKHK1 is caused by heterozygous variants in exons 30-31 of the CREBBP gene, whereas MKHK2 results from heterozygous variants in EP300 . Although these genes are classically associated with Rubinstein-Taybi syndrome (RTS), Menke-Hennekam syndrome presents a distinct phenotype despite involvement of the same alleles. We report 2 patients who exhibited developmental delay, intellectual disability, and dysmorphic features without typical RTS findings. Genetic analysis revealed a novel frameshift variant in EP300 in one patient and a de novo missense variant in CREBBP in the other. Long-term follow-up and increasing use of whole-exome sequencing have facilitated recognition of Menke-Hennekam syndrome as a distinct clinical entity. Reporting 2 patients with exon 31 variants in CREBBP and EP300 , we aim to improve awareness and diagnostic accuracy of this rare disorder.

Introduction: Klinefelter syndrome, the most common sex chromosome aneuploidy and a major genetic cause of male infertility, is also associated with systemic comorbidities, congenital anomalies, neurodevelopmental impairments, dysmorphic features, and an increased risk of certain malignancies. While the classical form is 47,XXY, mosaicism and higher-grade sex chromosome aneuploidies are also observed. This study aimed to evaluate the clinical and genetic characteristics of patients diagnosed with Klinefelter syndrome over a 25-year period at a single tertiary center and to compare findings across different karyotype groups. Methods: A total of 133 patients diagnosed with Klinefelter syndrome between January 2000 and September 2025 were retrospectively reviewed. Patients were categorized into three groups: 47,XXY; mosaic karyotypes; and higher-grade sex chromosome aneuploidies. Demographic, clinical, and reproductive characteristics were analyzed, and intergroup statistical comparisons were performed. Results: The majority of patients had a 47,XXY karyotype (87.2%), followed by mosaic forms (6.8%) and higher-grade sex chromosome aneuploidies (6%). Infertility was the most common presenting complaint (62.4%). The predominant clinical findings were hypoplastic or atrophic testes (68.3%), tall stature (15.8%), and gynecomastia (15.8%). Patients with higher-grade sex chromosome aneuploidies were diagnosed at younger ages and exhibited significantly higher rates of congenital anomalies, dysmorphic features, and neurodevelopmental impairment compared with those with the 47,XXY karyotype. Conclusion: Because most individuals with Klinefelter syndrome are diagnosed in adulthood following infertility evaluation and often display subtle manifestations in childhood, early recognition is essential. Increasing awareness of Klinefelter syndrome is crucial to ensure timely detection and management of associated comorbidities, particularly endocrine disorders.

Introduction: Phelan-McDermid syndrome (PMS) is a neurodevelopmental disorder most often caused by terminal 22q13.3 deletions involving SHANK3. Although primarily associated with developmental delay, hypotonia, and autism spectrum disorder-like features, rare reports have described atypical teratoid/rhabdoid tumor (AT/RT) in PMS, suggesting a potential oncogenic link. Case Presentation: We report the clinical, molecular, and treatment features of a child with PMS and AT/RT and review previously published cases. The proband presented with global developmental delay, absent speech, hypotonia, joint laxity, and characteristic dysmorphic features. Chromosomal microarray revealed a ∼2.26 Mb terminal deletion at 22q13.32q13.33, encompassing 31 OMIM-listed genes including SHANK3. At 6 months of age, he was diagnosed with AT/RT and treated with multimodal chemotherapy and craniospinal radiotherapy, achieving remission. Literature review identified additional PMS patients with AT/RT, supporting a role for 22q instability in tumorigenesis. Conclusion: This case highlights a rare but clinically significant association between PMS and AT/RT. Awareness of this potential link and careful radiotherapy planning are warranted to optimize outcomes in affected individuals.

Klinefelter syndrome is most commonly associated with a 47,XXY karyotype, though rarer variants such as 48,XXXY, 48,XXYY, 49,XXXXY, and mosaic forms occur. The clinical spectrum includes intellectual disability, psychiatric disorders, endocrinopathies, and infertility, while epilepsy is rarely reported. The syndrome is also linked to an increased risk of malignancies, including breast cancer and mediastinal germ cell tumors. Multinodular and vacuolating neuronal tumors (MVNTs) are rare glioneuronal neoplasms. We report a 9-year-old male with a two-year history of epilepsy, in whom brain MRI revealed an MVNT in the left posterior temporal lobe. Chromosomal microarray analysis showed a 2.5 Mb duplication at Xp22.33, a 152.9 Mb duplication from Xp22.33 to Xq28, and a 280 kb deletion at 5q33.1. Karyotyping confirmed a 47,XXY karyotype, consistent with Klinefelter syndrome. While MVNTs are typically sporadic or monogenic, this case raises the possibility of an association with Klinefelter syndrome. To our knowledge, this is the second reported case.