Expanding the phenotype of IFAP/BRESECK syndrome: A new case with severe hypogammaglobulinemia

• Published in: European journal of medical genetics Vol. 56; no. 11; pp. 603 - 605
• Main Authors: Corujeira, Susana, Águeda, Sofia, Monteiro, Georgina, Canelhas, Aurea, Sampaio, Mafalda, Rocha, Ruben, Leão, Miguel
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Masson SAS 01-11-2013
• Subjects: Agammaglobulinemia - diagnosis; Agammaglobulinemia - genetics; Brain - abnormalities; BRESEK/BRESHECK syndrome; Congenital Abnormalities - diagnosis; Congenital Abnormalities - genetics; Ear - abnormalities; Ectodermal Dysplasia - diagnosis; Ectodermal Dysplasia - genetics; Genetic Diseases, X-Linked - diagnosis; Genetic Diseases, X-Linked - genetics; Hirschsprung disease; Hirschsprung Disease - diagnosis; Hirschsprung Disease - genetics; Humans; Hypogammaglobulinemia; IFAP syndrome; Infant; Intellectual Disability - diagnosis; Intellectual Disability - genetics; Kidney - abnormalities; Male; MBTPS2; Medical Education; Metalloendopeptidases - genetics; Phenotype; Rectal fistula; IFAP syndrome; Hypogammaglobulinemia; Hirschsprung disease; MBTPS2; Rectal fistula; BRESEK/BRESHECK syndrome
• ISSN: 1769-7212; 1878-0849
• DOI: 10.1016/j.ejmg.2013.09.005

Abstract The ichthyosis follicular with atrichia and photophobia syndrome (IFAP) is a rare X-linked multiple congenital malformation syndrome. Some male patients have additional features including brain anomalies, intellectual disability, ectodermal dysplasia, skeletal deformities, ear or eye anomalies and kidney dysplasia/hypoplasia (BRESEK syndrome) sometimes associated with Hirschsprung disease and cleft palate or cryptorchidism (BRESHECK syndrome). We report a 5 months-old male patient with the p.R429H mutation in MBTPS2 protein, which has been reported to be associated with the most severe phenotype of patients with IFAP/BRESHECK syndrome. This patient presented with a severe IFAP/BRESHECK phenotype including ichthyosis follicular, atrichia, photophobia, brain anomalies, global developmental delay, Hirschsprung disease and kidney hypoplasia. Additional features not previously reported in IFAP syndrome, include severe hypogammaglobulinemia and congenital rectourethral fistula.