Bashar Sahar

Warsaw Breakage Syndrome (WABS) is a rare autosomal recessive chromosome instability disorder caused by biallelic pathogenic variants in DDX11 [1]. It is characterised by growth restriction, microcephaly, intellectual disability and sensorineural hearing loss [1,4,5]. We report a 21-year-old Sudanese woman with severe proportionate short stature, microcephaly, intellectual disability, hearing loss and pigmentary skin changes. Genetic testing identified a homozygous DDX11 missense variant (c.707A>G; p.His236Arg), classified as a variant of uncertain significance (VUS). Despite uncertain classification, the phenotype is highly suggestive of WABS. This case highlights the importance of clinical correlation in interpreting VUS findings in rare cohesinopathies [5,8].

Background: Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycaemia in children, most frequently caused by pathogenic variants in ABCC8 or KCNJ11, encoding subunits of the pancreatic KATP channel (1,3). Case presentation: A previously healthy 7-year-old boy presented with recurrent early morning hypoglycaemia associated with lethargy, sweating and confusion. Biochemical evaluation confirmed hyperinsulinaemic hypoglycaemia with suppressed ketones and free fatty acids. He responded completely to diazoxide, indicating functional KATP channel involvement. Whole-exome sequencing identified no clearly pathogenic variants but several variants of uncertain significance (VUS) in ABCC8, KCNJ11, and HNF1A, including a homozygous deep intronic variant (ABCC8: c.2256-50T>C) potentially affecting splicing (2,3). Outcome: The patient achieved full remission with diazoxide therapy, frequent carbohydrate intake, and bedtime cornstarch supplementation. Conclusion: This case illustrates the diagnostic complexity of CHI with multiple VUS and highlights the clinical utility of diazoxide responsiveness as a functional marker of KATP channel dysfunction. Functional studies of deep intronic variants and polygenic interactions remain essential for accurate molecular diagnosis (2,3).

Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Background: Precocious puberty (PP) implies the appearance of physical and hormonal signs of pubertal development at an earlier age what is considered normal. The beginning of puberty at an earlier age can have serious impact on the psychosocial wellbeing of the growing children in addition to its economic burden on the family. PP can be classified as central or peripheral depending on its etiology and many syndromes were identified for this growth disorder. The diagnosis of PP still represents a challenge to physicians and multidisciplinary approach is a key step to find out the correct etiology and to decide about long-term therapy. Case Report: We report a 7 year-old girl with history of prematurity presented with right sided hemihypertrophy of the body and accelerated linear growth confirmed with clinical examination and growth chart. All possible relevant laboratory and radiological tests performed to assess of her clinical condition. The diagnosis of central precocity associated with Silver-Russell Syndrome was suspected based on the clinical ground. Conclusions: PP with hemihypertrophy should be investigated thoroughly to look for central or peripheral etiology. Despite identifying many etiologies, our patient is the first case to report with these unique features.