American Journal of Medical and Biological Research, 2013, Vol. 1, No. 1, 33-36 DOI:10.12691/ajmbr-1-1-6 Prenatal Diagnosis of Osteopathia Striata with Cranial Sclerosis in a Male Fetus with a ~330kb Deletion of Xq11.1 Involving the WTX Gene Patrick L. Wilson 1,* , Ashley Davis 2 , Jean Ricci Goodman 1,4 , Lauren Notley 1 , Shibo Li 2 , Ji-Yun Lee 2,5 , Zhongxin Yu 3 , Klaas J. Wierenga 2 , Andrew F. Wagner 1 1 Department of Obstetrics and Gynecology, Maternal/Fetal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, USA 2 Department of Pediatrics, Genetics Section, University of Oklahoma Health Sciences Center, Oklahoma City, USA 3 Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, USA 4 Deparment of Obstetrics and Gynecology, Maternal/Fetal Medicine, Loyola University, Stritch School of Medicine, Chicago, USA 5 Department of Pathology, Korea University, Seoul, Korea *Corresponding author: Patrick-L-Wilson@ouhsc.edu Received December 29, 2012; Revised February 15, 2013; Accepted February 16, 2013 Abstract Osteopathia striata with cranial sclerosis (OSCS) is a rare X-linked dominant genetic disorder resulting mutation in the WTX gene. Clinically, OSCS presents with linear striations in the metaphyseal region of the long bones and pelvis in combination with sclerosis of the cranium and face. A twenty-seven year old G5T1P3A0L2 woman with a history of peri- and neonatal infant male deaths was referred to us at 22 weeks, 6 days into her recent pregnancy. Ultrasound evaluation identified a male fetus, bilaterally enlarged lateral ventricles, a cloverleaf skull, suspected bilateral cleft lip, nuchal thickening, bilateral bowed radii and ulnae, gastroschisis with herniated viscera, bilateral absent fibula and clubfeet. The results of prenatal testing identified a male fetus with a 330kb Xq11.1 deletion involving the entire WTX gene. Initial microarray analysis of maternal blood identified a normal female karyotype, 46,XX. FISH analysis with a BAC clone mapped to the WTX gene identified low-level mosaicism in blood and buccal samples, 17% and 15%, respectively, which explained the negative maternal microarray result. Keywords: Osteopathia striata with cranial sclerosis (OSCS), Wilms tumor on the X-chromosome (WTX) gene, Microarray, Mosaic, Osteopetrosis, Germline mosaicism 1. Introduction Osteopetrosis, or “marble bone disease,” refers to a group of rare heritable, skeletal disorders. Phenotypically, there is an increase in bone density on radiographs which is due to a failure of osteoclasts to differentiate or function properly [1]. A subtype of osteopetrosis is osteopathia striata with cranial sclerosis (OSCS), which is a rare genetic disorder that is most often seen with X-linked inheritance patterns. Clinically, OSCS presents with longitudinal striations of osteosclerosis in the long bones. More importantly, OSCS presents with osteosclerosis in the bones of the cranium and face. This type of osteosclerosis leads to disfigurement and increased pressure on the cranial nerves, which leads to disabilities, e.g. deafness. OSCS has phenotypic variability in females and male. In females, OSCS features are macrocephaly, cleft palate, mild learning disabilities, sclerosis of the long bones and skull and longitudinal striations. For males, OSCS causes fetal or neonatal death. Males that do survive have the features of females with OSCS along with hyperostosis, cardiac, intestinal and genitourinary malformations [2,3]. Other features of OSCS may include: clubfoot; small ventricular septal defects, aortic stenosis; clinodactyly; dental and visual problems; hydrocephalus; hypertelorism, flat nasal bridge; scoliosis of the back; long fingers, facial nerve palsy; and mild mental retardation. The gene responsible for OSCS has been mapped to the locus Xq11.1. The phenotype is thought to be due to a mutation in the WTX gene. WTX, also referred to as Wilms Tumor Gene on the X Chromosome, is a 7.5 Kb transcript that encodes for a protein that consists of 1,135 amino acids. If the WTX gene is mutated, WNT signaling will increase. Therefore, WTX normally acts as a repressor of canonical WNT signaling [4]. Here, we report a case of osteopathia striata with cranial sclerosis in a male baby. The mother had two previous pregnancies in which the male fetus had multiple anomalies. 2. Case Presentation The patient originally presented to us during her first pregnancy in 2002 at 27-6/7 weeks gestation because of anhydramnios and abnormal outside ultrasound. The ultrasound identified a male fetus with, frontal bossing, mild hydrocephalus, short limbs, indeterminate hands and feet, a small chest, and kidneys that were dilated and echogenic. At 29 weeks, the patient was diagnosed with eclampsia and delivered her son via cesarean section.