CLINICAL REPORT Frontonasal Dysplasia, Callosal Agenesis, Basal Encephalocele, and Eye Anomalies Syndrome With a Partial 21q22.3 Deletion Maria Leine Guion-Almeida, 1 * Antonio Richieri-Costa, 1 Fernanda Sarquis Jehee, 2 Maria Rita Santos Passos-Bueno, 2 and Roseli Maria Zechi-Ceide 1 1 Department of Clinical Genetics, Hospital for Rehabilitation of Craniofacial Anomalies (HRAC), University of S~ ao Paulo, Bauru, SP, Brazil 2 Human Genome Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of S~ ao Paulo, S~ ao Paulo, SP, Brazil Manuscript Received: 10 August 2011; Manuscript Accepted: 30 January 2012 We describe a girl with a phenotype characterized by frontonasal dysplasia, callosal agenesis, basal encephalocele, and eye anoma- lies who presents a 46,XX,r(21) karyotype. Array-comparative genomic hybridization using the Afflymetrix 100K DNA oligoar- ray set showed an interstitial deletion 21q22.3 of approximately 219 kb. Conventional karyotype of both parents was normal, and it was not possible to perform the molecular studies. In this report we raise the hypothesis that the deleted genes located at 21q22.3 could account to the phenotype. Ó 2012 Wiley Periodicals, Inc. Key words: frontonasal dysplasia; CNS midline anomalies; basal encephalocele; 21q22.3 deletion INTRODUCTION Frontonasal dysplasia (FND) is a genetically heterogeneous group of disorders with abnormal frontonasal process development. It has been reported, most of the times, as an isolated field defect [Sedano and Gorlin, 1988]. The involvement of other additional fields have been resulted in a growing number of different syndromes described within the spectrum of the FND and, some of these syndromes support a known genetic pattern of inheritance while others have been reported as unique or recurrent pattern syn- dromes [revised by Wu et al., 2007]. One of the syndromes within this spectrum comprises the syndrome of midline facial defects, basal encephaloceles, callosal agenesis, and eye anomalies, recog- nized as a distinct entity [Leitch and Winter, 1996; Lees et al., 1998]. Here we describe and discuss the clinical and the molecular findings of a girl with this condition, who was previously evaluated within a sample of patients (case 6) with similar phenotype [Richieri-Costa and Guion-Almeida, 2004]. CLINICAL REPORT A girl (Fig. 1A–C) was referred to our Hospital at the age of 6 months for assessment and management of median cleft lip. She was the first child and the mother had a previous pregnancy which resulted in a miscarriage of unknown cause and two other normal girls. The parents were non-consanguineous and phenotypically normal. The pregnancy was unremarkable with no exposure to known teratogens. Delivery was at term, by cesarean; birth weight and length were not recorded. At birth she was noted to have a median cleft lip. Examination at age 6 months showed weight of 6.6 kg (10th centile), length of 61 cm (3rd centile), OFC of 42 cm (50th centile), inner canthal distance of 3.2 cm (>97th centile), and outer canthal distance of 8.1 cm (97th centile). She had prominent frontal, hypertelorism, left palpebral ptosis, broad nasal root, and incomplete median cleft lip with median alveolar notch. Upper and lower limbs were normal. The follow up showed weight and height below the normal ranges and normal neuropsychological development but with mild learning disabilities. Ophthalmic examination with fundoscopy was normal. Audiological evaluation was normal. Endocrinological evaluation detected GH and TSH deficiency. Cranial CT and MRI scans demonstrated a large sphenoethmoidal encephalocele extending in direction to the nasopharinx with part of the anterior frontal lobe projecting through it; mild enlargement of the lateral ventricles; callosal Grant sponsor: CNPq; Grant numbers: 301789/2009-6, 302712/2010-0. *Correspondence to: Maria Leine Guion-Almeida, PhD, HRAC-USP, Rua Silvio Marchione 3-20, CEP 17012-900, Bauru, SP, Brazil. E-mail: mlguion@usp.br Article first published online in Wiley Online Library (wileyonlinelibrary.com): 24 May 2012 DOI 10.1002/ajmg.a.35351 How to Cite this Article: Guion-Almeida ML, Richieri-Costa A, Jehee FS, Passos-Bueno MRS, Zechi-Ceide RM. 2012. Frontonasal dysplasia, callosal agenesis, basal encephalocele, and eye anomalies syndrome with a partial 21q22.3 deletion. Am J Med Genet Part A 158A:1676–1679. Ó 2012 Wiley Periodicals, Inc. 1676