title: Further delineation of the phenotype of severe congenital neutropenia type 4 due to mutations in G6PC3.
abstract: Severe congenital neutropenia type 4 (SCN4) is an autosomal recessive condition, which was defined recently with identification of the causative mutations in G6PC3. To date there are only three reports in the literature describing patients with SCN4 with mutations in the G6PC3 gene. We report four individuals with SCN4 who belong to a single large consanguineous kindred. We provide an overview of the non-haematological features of the condition with a focus on the adult phenotype, which has not been previously described in detail. We show that the superficial venous changes seen in SCN4 patients can develop into varicose veins and venous ulcers in adulthood. We review the range of congenital anomalies associated with SCN4. We demonstrate that secundum atrial septal defect, patent ductus arteriosus and valvular defects are the most frequent cardiac anomalies in SCN4. Drawing parallels with type 1 glycogen storage disease, we propose that poor growth of prenatal onset, mild-to-moderate learning disability, primary pulmonary hypertension, delayed or incomplete puberty, hypothyroidism and dysmorphism likely represent features of this syndrome. We also suggest monitoring for lipid anomalies, and kidney and liver function in affected patients. Delineation of the SCN4 phenotype may help in appropriate treatment and management and provide further insights into the pathogenesis of this multisystem disease.
authors: Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), University of Manchester, St Mary's Hospital, Manchester, UK. Siddharth.Banka@manchester.ac.uk
authors: Siddharth
authors: S
authors: Banka
authors: Elena
authors: E
authors: Chervinsky
authors: William G
authors: WG
authors: Newman
authors: Yanick J
authors: YJ
authors: Crow
authors: Shay
authors: S
authors: Yeganeh
authors: Joanne
authors: J
authors: Yacobovich
authors: Dian
authors: D
authors: Donnai
authors: Stavit
authors: S
authors: Shalev
mesh_terms: D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D000080984:Congenital Bone Marrow Failure Syndromes; D003241:Consanguinity; D002658:Developmental Disabilities / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D005952:Glucose-6-Phosphatase / Q000235:genetics*; D005953:Glycogen Storage Disease Type I / Q000235:genetics; D006330:Heart Defects, Congenital / Q000235:genetics; D006801:Humans; D007859:Learning Disabilities / Q000235:genetics; D008297:Male; D009154:Mutation; D009503:Neutropenia / Q000151:congenital / Q000235:genetics / Q000503:physiopathology; D010375:Pedigree; D010641:Phenotype
chemical_list: D005952:Glucose-6-Phosphatase; C492193:G6PC3 protein, human