Aug 2026· Turkish Journal of Pediatrics· 0 citations· 29 references
Abstract
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.
King–Denborough syndrome is a rare RYR1-related congenital myopathy characterized by dysmorphic features, muscle weakness, and susceptibility to malignant hyperthermia, often posing a diagnostic challenge in early infancy. We report a one-year-old female child presenting with developmental delay and generalized hypotonia. Clinical evaluation revealed craniofacial dysmorphism, bilateral ptosis, and esotropia, raising suspicion of an underlying congenital myopathy. Initial laboratory and imaging workup were inconclusive except for transient elevation of creatine kinase. Whole exome sequencing identified a heterozygous missense variant in the RYR1 gene (c.14126C>T; p.Thr4709Met), along with a likely pathogenic FOXP1 variant. In view of the characteristic clinical phenotype, a diagnosis of King–Denborough syndrome was considered. The child was managed with supportive therapy and developmental interventions, and caregivers were counselled regarding the risk of malignant hyperthermia. This case underscores the importance of clinicogenetic correlation in diagnosing rare myopathies and highlights the need for early recognition to enable appropriate counselling and prevention of anaesthetic complications.
Ariya Venu, Reshma Anna Philip, Joseline Joseph et al.· International Journal of Con...· 0 citations
Schwartz-Jampel Syndrome (SJS) is a rare autosomal recessive disorder characterised by myotonia, craniofacial dysmorphism and skeletal dysplasia, resulting from pathogenic variants in Heparan Sulfate Proteoglycan 2 (HSPG2). Pathogenic variants disrupt perlecan function, resulting in abnormal cartilage development and impaired neuromuscular transmission. A three-year and fivemonth-old male presented with blepharophimosis, generalised muscle stiffness, delayed motor milestones and gait abnormality. Electromyography demonstrated continuous spontaneous myotonic discharges. Radiographs revealed metaphyseal dysplasia with epiphyseal abnormalities. Molecular testing identified three heterozygous HSPG2 variants with parental carrier status, consistent with compound heterozygosity. Carbamazepine and structured rehabilitation were administered. Follow-up demonstrated reduction in myotonia, improved gait parameters and decreased fall frequency. In early-onset myotonic disorders, SJS should be considered with characteristic craniofacial and skeletal features. Symptomatic treatment with sodium-channel–blocking agents and multidisciplinary rehabilitation may confer functional benefit.
Komal J Rathod, P. S. Parihar, Ramesh Chaple et al.· Journal of Clinical and Diag...· 0 citations
Sotos syndrome is an overgrowth disorder caused by heterozygous NSD1 variants, partial-gene deletions, or 5q35 microdeletions. Malan syndrome, a phenotypically overlapping condition, results from haploinsufficiency of the NFIX gene due to either heterozygous chromosomal microdeletions involving the 19p13.2 region or heterozygous loss-of-function variants. This multicenter study aimed to characterize the clinical and molecular features of individuals with Sotos and Malan syndromes in Türkiye. We retrospectively analyzed clinical and molecular data from 48 individuals with genetically confirmed Sotos or Malan syndrome across 14 centers. Molecular analyses included whole-exome sequencing, clinical exome sequencing, targeted gene panels, multiplex ligation-dependent probe amplification, and chromosomal microarray analysis. Forty-two individuals were diagnosed with Sotos syndrome and six with Malan syndrome. All exhibited characteristic facial features, and 97.9% had developmental delay or intellectual disability. We identified a total of 38 NSD1 variants, of which 35 were classified as pathogenic or likely pathogenic and three as variants of uncertain significance; notably, 23 of these variants were novel. Three patients carried 5q35 microdeletions, and one had an intragenic deletion involving exons 10-11. Four distinct NFIX variants (two novel) were detected in five patients, and one carried a 19p13.13 deletion encompassing the entire gene. This nationwide study expands the genotype-phenotype spectrum of Sotos and Malan syndromes in Türkiye and supports improved diagnostic and clinical management strategies.
Ceren Yılmaz Uzman, S. Gürsoy, F. Hazan et al.· Clinical Genetics· 0 citations
Background KBG syndrome (KBGS) is a rare autosomal dominant neurodevelopmental disorder caused by heterozygous pathogenic variants in ANKRD11. It is characterized by developmental delay, intellectual disability, behavioral difficulties, macrodontia, craniofacial dysmorphism, short stature, and skeletal anomalies. Objectives To describe the clinical, radiological, and molecular findings of Saudi patients with molecularly confirmed KBGS and compare their presentation with reported features in the literature. Methods We conducted a retrospective case series at King Faisal Specialist Hospital and Research Centre, Riyadh, between January 2002 and December 2024. Clinical, dysmorphological, developmental, behavioral, family history, neuroimaging, and molecular data were reviewed for three pediatric patients with confirmed ANKRD11-related KBGS. Results All patients demonstrated core features of KBGS, including intellectual disability, speech and motor delay, learning difficulties, and behavioral manifestations such as autism spectrum features or aggression. Common dysmorphic findings included long philtrum and prominent ears in all patients, with a triangular face, macrodontia, and synophrys observed in two patients. Short stature and skeletal anomalies were also present. Molecular testing identified heterozygous pathogenic or likely pathogenic ANKRD11 variants: NM_013275.6:c.4087C > T (p.Arg1363Ter), NM_013275.6:c.3382_3383del (p.Asp1128GlufsTer41), and NM_013275.6:c.1977C > G (p.Tyr659Ter). All variants were predicted to result in premature termination. Renal fusion and complex vertebral anomalies were observed, suggesting possible underrecognized systemic involvement, although cautious interpretation is required given the small sample size. Conclusion This Saudi case series adds to the growing evidence of clinical heterogeneity in KBGS. Early recognition, molecular confirmation, multidisciplinary care, and longitudinal follow-up are essential to improve diagnosis, surveillance, and management.
Mai S. Labani, Z. Rahbeeni· Frontiers in Pediatrics· 0 citations
This study expands the mutational landscape of JS in the Iranian population and underscores the utility of WES as a first-tier diagnostic tool for JS and related ciliopathies.
Sheyda Khalilian, Mohadeseh Fathi, Zahra Farbood et al.· Molecular Genetics and Metab...· 0 citations
A novel homozygous missense variant in RNF216 gene c.1055T>G (p.(Phe352Cys)) in three siblings with Gordon Holmes syndrome is reported, contributing to the limited knowledge of GHS and highlighting the importance of hypogonadotropic hypogonadism treatment and close observation of neurological symptoms that may develop over time.
