title: Osteopathia striata cranial sclerosis: non-random X-inactivation suggestive of X-linked dominant inheritance.
abstract: Osteopathia striata with cranial sclerosis (OS-CS) is a rare syndrome comprising macrocephaly, minor anomalies, conductive hearing loss, and mild mental retardation. The diagnosis is based on radiological findings, including cranial sclerosis and longitudinal striations of metaphyses of long bones. Here we report on 10 new cases of OS-CS, including two sporadic cases and three families, with an excess of affected females (9F/1M). Phenotypic variability was observed in our patients as well as several unusual findings. Hirschsprung disease, Pierre Robin sequence, coronal craniostenosis, and laryngotracheomalacia were associated with a poor prognosis. The X-inactivation pattern of peripheral blood lymphocytes in a mildly affected mother and her severely affected boy demonstrated a non-random X-inactivation in the mother. This finding, in combination with a sex ratio in favor of females and an increased morbidity and mortality in males, is highly suggestive of X-linked dominant inheritance.
authors.affiliation: Department of Genetics, Hôpital Necker-Enfants Malades, Paris, France. geraldine.viot@cch.ap-hop-paris.fr
authors.forename: Géraldine
authors.initials: G
authors.lastname: Viot
authors.forename: Didier
authors.initials: D
authors.lastname: Lacombe
authors.forename: Albert
authors.initials: A
authors.lastname: David
authors.forename: Michèle
authors.initials: M
authors.lastname: Mathieu
authors.forename: Alain
authors.initials: A
authors.lastname: de Broca
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.forename: Nadine
authors.initials: N
authors.lastname: Gigarel
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Stanislas
authors.initials: S
authors.lastname: Lyonnet
authors.forename: Martine
authors.initials: M
authors.lastname: Le Merrer
authors.forename: Valérie
authors.initials: V
authors.lastname: Cormier-Daire
mesh_terms: D000015:Abnormalities, Multiple / Q000000981:diagnostic imaging / Q000235:genetics*; D001848:Bone Diseases, Developmental / Q000000981:diagnostic imaging / Q000235:genetics*; D004303:Dosage Compensation, Genetic; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D010026:Osteosclerosis / Q000000981:diagnostic imaging / Q000235:genetics; D010375:Pedigree; D011859:Radiography; D012886:Skull / Q000002:abnormalities; D013577:Syndrome