title: Boy with pseudohypoparathyroidism type 1a caused by GNAS gene mutation (deltaN377), Crouzon-like craniosynostosis, and severe trauma-induced bleeding.
abstract: We report on a 6-month-old boy with craniosynostosis, pseudohypoparathyroidism type 1a (PHP1A), and a GNAS gene mutation. He had synostoses of the coronal, frontal, and sagittal sutures, brachyturricephaly, and hydrocephaly. He also had congenital hypothyroidism, round face, full cheeks, shortness of limbs, mild developmental delay, and muscular hypotonia. Because of progressive hydrocephaly, the synostosis was corrected surgically but circulatory decompensation led to disseminated intravascular coagulation and cerebral infarctions. Our patient died 8 days later. Postmortem molecular studies of GNAS, the gene for guanine nucleotide-binding protein, alpha-stimulating activity polypeptide (gene for PHP1A), identified a de novo heterozygous 3 bp in frame deletion predicting a deletion of the asparagine residue at position 377 (deltaN377). This is the second report of this mutation. Results of molecular studies of craniosynostosis genes (FGFR2, FGFR3) and of numerous genetic variants predisposing to bleeding disorders were normal. We question whether craniosynostosis and trauma-induced bleeding disorder may be manifestations of PHP1A, or if our patient had two or three different congenital disorders.
authors.affiliation: Institute of Medical Genetics, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Luitgard M
authors.initials: LM
authors.lastname: Graul-Neumann
authors.forename: Alexia
authors.initials: A
authors.lastname: Bach
authors.forename: Michael
authors.initials: M
authors.lastname: Albani
authors.forename: Hannelore
authors.initials: H
authors.lastname: Ringe
authors.forename: Andreas
authors.initials: A
authors.lastname: Weimann
authors.forename: Wolfram
authors.initials: W
authors.lastname: Kress
authors.forename: Olaf
authors.initials: O
authors.lastname: Hiort
authors.forename: Oliver
authors.initials: O
authors.lastname: Bartsch
mesh_terms: D001930:Brain Injuries / Q000150:complications*; D002864:Chromogranins; D003409:Congenital Hypothyroidism / Q000150:complications; D003394:Craniofacial Dysostosis / Q000150:complications / Q000235:genetics* / Q000601:surgery; D017809:Fatal Outcome; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D006849:Hydrocephalus / Q000150:complications / Q000209:etiology; D007223:Infant; D020300:Intracranial Hemorrhages / Q000150:complications* / Q000235:genetics; D008297:Male; D009154:Mutation; D011547:Pseudohypoparathyroidism / Q000150:complications / Q000235:genetics*
chemical_list: D002864:Chromogranins; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs