Journal of Pediatric Genetics - Volume 2, issue 4

Authors: Vendramini-Pittoli, Siulan | Guion-Almeida, Maria L. | Richieri-Costa, Antonio | Santos, Juliana M. | Kokitsu-Nakata, Nancy M.

Article Type: Research Article

Abstract: The authors describe the clinical findings of 38 children with congenital anomalies and misoprostol intrauterine exposure. This study included 38 cases, ascertained from case series of the Hospital of Rehabilitation of Craniofacial Anomalies from University of São Paulo, with evidence of intrauterine exposure to misoprostol in the first trimester of the pregnancy. Information about misoprostol intake and drug administration route was obtained through interviews with mothers. Clinical evaluation showed 18 individuals with facial phenotype compatible with Moebius syndrome; 11 individuals with multiple congenital anomalies; and nine individuals with nonsyndromic cleft lip and/or cleft palate. This study showed a widening of …the phenotypic spectrum associated with misoprostol embryotoxicity. Show more

Keywords: Misoprostol exposure, cranial nerve palsy, congenital anomalies, cleft lip and palate, first and second pharyngeal arches, central nervous system anomalies

DOI: 10.3233/PGE-13066

Citation: Journal of Pediatric Genetics, vol. 2, no. 4, pp. 173-180, 2013

Authors: Chida, Ayako | Shintani, Masaki | Wakamatsu, Hajime | Tsutsumi, Yoshiyuki | Iizuka, Yuo | Kawaguchi, Nanako | Furutani, Yoshiyuki | Inai, Kei | Nonoyama, Shigeaki | Nakanishi, Toshio

Article Type: Research Article

Abstract: Although mutations in the RASA1 gene in vein of Galen aneurysmal malformation (VGAM) and an endoglin gene mutation in a VGAM patient with a family history of hereditary hemorrhagic telangiectasia (HHT) have been identified, most VGAM cases have no mutation in these genes. We sought to detect mutations in other genes related to HHT. We screened for mutations in RASA1 and three genes (endoglin, activin receptor-like kinase 1 (ACVRL1), encoding ALK1, and SMAD4 ) related to HHT in four VGAM patients. One variant (c.652 C>T p.R218W) in ACVRL1 was identified. Immunoblotting revealed that the ALK1-R218W …protein could not promote SMAD1/5/8 phosphorylation by BMP9 stimulation. On the other hand, wild-type ALK1 could enhance the phosphorylation as expected. Furthermore, the transcriptional activation of ALK1-R218W was less efficient than that of wild-type ALK1. We identified 1 variant in ACVRL1 in a VGAM patient. These findings suggest that the ACVRL1 variant-R218W may be associated with the pathogenesis of VGAM. Show more

Keywords: ACVRL1, gene variant, vein of Galen aneurysmal malformation

DOI: 10.3233/PGE-13067

Citation: Journal of Pediatric Genetics, vol. 2, no. 4, pp. 181-189, 2013

Authors: Lamichhane, MD, Dronacharya

Article Type: Research Article

Abstract: Prevalence of intellectual disability (ID) varies from 1–3%. Genetic causes of ID are being increasingly recognized. Although multiple mutations have been identified as a cause of syndromic ID, the genetic etiology of non-syndromic ID is poorly understood. However, more than 100 loci have been mapped that are associated with non-syndromic ID. There have been a couple of reports of AP4B1 gene mutation causing severe intellectual disability, absent speech, shy character, stereotypic laughter, muscular hypotonia that progressed to spastic paraplegia, microcephaly, foot deformity, decreased muscle mass of the lower limbs, inability to walk, and growth retardation. They had structural brain abnormalities …and seizures. The reported cases were from Arab families where consanguineous marriage is common. We encountered an African-American child who presented first at the age of 24 mo with language difficulties and was subsequently found to have moderate to severe intellectual disability by standardized tests. Shortly, he started to have seizures and problems with ambulation. Although he was hypotonic at the time of presentation, legs slowly became spastic at the age of 4 yr. After a thorough work up, he was found to have heterozygous mutation in the AP4B1 gene along with another missense mutation in the same gene. There has been no report of mutation in this gene in the North American population. Although AP4B1 typically is said to be an autosomal recessive disease-causing gene, our case is different in the sense that there are two mutations in the same gene one of which has never been reported before and co-exists with a known disease causing mutation. Yet, the phenotype of the case closely resembles those published previously. Show more

Keywords: Intellectual disability, AP4B1, hereditary spastic paraplegia

DOI: 10.3233/PGE-13068

Citation: Journal of Pediatric Genetics, vol. 2, no. 4, pp. 191-195, 2013

Authors: Udayakumar, Achandira M. | Al-Kindy, Adila

Article Type: Other

Abstract: Trisomy 8 mosaicism (Warkany syndrome) is a rare viable condition with variable phenotypes, ranging from mild dysmorphic features to severe malformations. Karyotyping and fluorescence in-situ hybridization potentially help detecting this low mosaic clone to confirm the diagnosis of patients with classical and unusual clinical presentations. This report reviews few previous cases to describe our case - a boy who had trisomy 8 mosaicism with severe dysmorphic features, born to a consanguineous Arabic couple. This study concludes that careful cytogenetic diagnoses of trisomy 8 mosaicism is essential for appropriate management and follow up of this rare disorder.

Keywords: Dysmorphic features, FISH, trisomy 8 mosaicism, Warkany syndrome

DOI: 10.3233/PGE-13069

Citation: Journal of Pediatric Genetics, vol. 2, no. 4, pp. 197-201, 2013

Authors: Westberry, David | Pugh, Linda

Article Type: Other

Abstract: Zellweger spectrum disorders result from defects in the assembly of the peroxisome and are sometimes referred to as peroxisome biogenesis disorders. Orthopedic manifestations of this condition are variable. This case report illustrates an ambulatory child with Zellweger syndrome and progressive foot deformity. The course of treatment consisted of initial soft tissue surgery, early recurrence of the deformity, followed by successful arthrodesis.

Keywords: Zellweger, peroxisomal biogenesis disorder

DOI: 10.3233/PGE-13070

Citation: Journal of Pediatric Genetics, vol. 2, no. 4, pp. 203-207, 2013

Article Type: Other

Citation: Journal of Pediatric Genetics, vol. 2, no. 4, pp. 209-211, 2013

Article Type: Other

Citation: Journal of Pediatric Genetics, vol. 2, no. 4, pp. 213-214, 2013