A novel Xp22.11 deletion causing a syndrome of craniosynostosis and periventricular nodular heterotopia

• Published in: American journal of medical genetics. Part A Vol. 155A; no. 12; pp. 3144 - 3147
• Main Authors: van Kogelenberg, Margriet, Lerone, Margherita, De Toni, Teresa, Divizia, Maria T., de Brouwer, Arjan P.M., Veltman, Joris A., van Bokhoven, Hans, Robertson, Stephen P.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.12.2011; Wiley-Liss; Wiley Subscription Services, Inc
• Subjects: Biological and medical sciences; Child; Child, Preschool; Choline-Phosphate Cytidylyltransferase - genetics; Chromosome Deletion; Chromosomes, Human, X; Cortex; Craniosynostoses - diagnosis; Craniosynostoses - genetics; Craniosynostosis; Diseases of the osteoarticular system; Facies; Fontaine-Farriaux syndrome; genomics; Hemizygosity; Humans; Infant; Infants; Kruppel-Like Transcription Factors - genetics; Male; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Medical genetics; Medical sciences; Neurodevelopmental disorders; periventricular nodular heterotopia; Periventricular Nodular Heterotopia - diagnosis; Periventricular Nodular Heterotopia - genetics; Phenotype; Protein-Serine-Threonine Kinases - genetics; Syndrome; Ventricle (lateral); X chromosomal interstitial deletion; X-chromosome inactivation; Chromosomal aberration; X chromosomal interstitial deletion; Nervous system diseases; Craniosynostosis; Diseases of the osteoarticular system; periventricular nodular heterotopia; Skull disease; Deletion; Dysostosis; Interstitial; Fontaine—Farriaux syndrome
• ISSN: 1552-4825; 1552-4833; 1552-4833
• DOI: 10.1002/ajmg.a.34311

We report on a follow‐up evaluation of a male with a phenotype including craniosynostosis, periventricular nodular heterotopia, and neurodevelopmental delay. He was initially assigned a clinical diagnosis of Fontaine–Farriaux syndrome (FFS) as an infant although now, with improved delineation of this entity, it is evident that this diagnosis is not applicable to this individual. Array comparative genomic hybridization has demonstrated a 300 kb interstitial deletion on Xp22.11 affecting all or part of three annotated genes, ZFX, PDK3, and PCYT1B in this subject. The deletion was inherited from the phenotypically normal mother who also exhibited markedly skewed X‐inactivation. These findings implicate hemizygosity for one or all three of these genes as the cause of this phenotype. © 2011 Wiley Periodicals, Inc.