Hindawi Publishing Corporation Case Reports in Genetics Volume 2013, Article ID 504695, 4 pages http://dx.doi.org/10.1155/2013/504695 Case Report A Male with Cooccurrence of Down Syndrome and Fragile X Syndrome Tovi Anderson,1 Allison Buterbaugh,1 Kaitlin Love,2 and Jeannie Visootsak1 1 Emory University, Department of Human Genetics, 2165 N. Decatur Road, Decatur, GA 30033, USA 2 Florida State University College of Medicine, Tallahassee, FL 32304, USA Correspondence should be addressed to Jeannie Visootsak; [email protected] Received 24 May 2013; Accepted 4 August 2013 Academic Editors: S. Ennis and P. Saccucci Copyright © 2013 Tovi Anderson et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Down syndrome is the most common identifiable genetic cause of intellectual disability, with a unique physical gestalt that makes diagnosis possible during the newborn period. However, the physical characteristics of Fragile X syndrome are fairly subtle, resulting in the first clinical suspicion often arising from delayed developmental milestones. In addition, maladaptive behavior and autistic- like tendencies, such as hand flapping, poor eye contact, and hand biting, may be noted in Fragile X syndrome but are notas commonly observed in Down syndrome. Recognition of a potential secondary diagnosis, such as Fragile X syndrome, in individuals with Down syndrome is critical because there have been advances in targeted pharmacologic treatments for both conditions. Thus, an accurate diagnosis has implications in improving the individual’s quality of life. 1. Introduction hyperactivity, impulsivity, and aggressive behavior can also be present [5]. Down syndrome (DS, OMIM #190685), or trisomy 21, is The cooccurrence of DS and FXS in females has been the most common genetic cause of intellectual disability. reported in two cases prior to the identification of the FMR1 Brachycephaly with flat occiput, epicanthal folds and upslant- gene in 1991 [7, 8]. Additionally, there has been one case ing palpebral fissures, Brushfield spots in the iris, low nasal reportofamalewithbothDSandFXS[6]. Herein, we bridge, downturned mouth with protruding tongue, low-set present the second case of a male with both DS and full ears, broad neck, and small hands with transverse crease mutation FXS, illustrating the importance of investigating arecommonfeaturesinDS[1]. Since the physical gestalt is additional diagnoses when a DS diagnosis does not appropri- straightforward, individuals with DS are typically diagnosed ately explain the degree of intellectual disability and/or when in the newborn period. there are other family members with developmental delay. The physical features of Fragile X syndrome (FXS, OMIM Additionally, confirmation of a diagnosis of DS and/or FXS #300684) are often subtle; hence, clinical indication is based is critical, as a number of promising targeted treatments to on an array of intellectual and emotional disabilities ranging improve neurodevelopmental and behavioral outcomes for from learning problems and autism to anxiety. Families both conditions are undergoing clinical trials. typically become concerned about the child’s development at an average age of 13 months, and a FXS diagnosis occurs at an average age of approximately 32 months [2]. The 2. Clinical Report behavioral phenotype commonly associated with FXS may be helpfulinsuggestingthediagnosis.Forinstance,autistic-like The patient was born at 41 weeks gestation by spontaneous features, such as hand flapping, hand biting, gaze avoidance, vaginaldeliverywithabirthweightof4.16kg(>90th per- tactile defensiveness, and hyperarousal to sensory stimuli, are centile), length of 51 cm (>90th percentile), and head circum- common in individuals with FXS [3, 4]. Additionally, anxiety, ference of 33.5 cm (25th–50th percentile). Pregnancy history 2 Case Reports in Genetics were identified by PCR and Southern blot analysis. The mother has 120 CGG repeats based on PCR analysis. The patient’s other half-siblings have not been tested for FXS. The patient’s maternal grandmother is known to have attention deficit disorder, and the maternal grandfather is known to have dyslexia. The maternal grandmother reportedly has five nephews with FXS who are in their thirties. On physical examination at the age of 8 years and 11 months, weight is 18.5 kg (<5th centile on the regular and DS growth charts), height is 102 cm (<5th centile on the regular and DS growth charts), and head circumference is 46 cm (<5th centile on the regular and DS growth charts). He is a thin boy with low tone and hyperextensible joints. He has typical features of DS, including dolichocephaly, epicanthal Figure 1: Boy with cooccurrence DS and full mutation FXS. Features folds, upslanting palpebral fissures, and cutis laxa with promi- include dolichocephaly, epicanthal folds, and upslanting palpebral nent hand and foot creases. The right ear length is 5.5 cm fissures. (25th–50th percentile on a regular ear length chart; >50th percentile on a DS ear length chart) and left ear is 5.1 cm (10th percentile on a regular ear length chart; >50th percentile on was unremarkable. The clinical features of DS were recog- a DS ear length chart). nized shortly after birth, including the following features; Developmental outcomes are assessed at a chronological upslanting palpebral fissures, flat occiput, small nose, short age of 8 years and 11 months using the Vineland Adaptive neck with increased nuchal skin, clinodactyly of 5th fingers, Behavior Scales, Second Edition [9]. The Vineland Scales short fingers, increased space between first and second toes assess personal and social sufficiency across three domains of bilaterally, and hypotonia (Figure 1). A karyotype confirmed functioning (mean score of 100 and standard deviation ± 15): the diagnosis of trisomy 21. The echocardiogram revealed a Communication, Daily Living Skills, and Socialization. patent ductus arteriosus and ventricular septal defect. The Results from the Vineland Scales reveal a Communication patient was also diagnosed with Hirschsprung disease. score of 43 (expressive language age equivalent of 6 months, Past medical history is remarkable for feeding difficulties, receptive language age equivalent of 9 months), a Daily Living poor weight gain, hip dysplasia and neuromuscular hip Skills score of 48, a Socialization score of 50, a Motor score of dislocation, myringotomy for chronic otitis media, and ade- 40 (gross motor age equivalent of 8 months, fine motor age noidectomy and tonsillectomy for chronic upper respiratory equivalent of 11 months), and an Adaptive Behavior score of infections. Vision, hearing, and thyroid function tests have 46. The motor score is the lowest, as the patient continues to been normal. have muscular hypotonia and ligamentous hyperlaxity and is Developmental milestones were delayed, including sitting unable to ambulate independently. at 7 months and crawling at 8 months. He currently does not The Child Behavior Checklist (CBCL) asks the parents ambulate independently and continues to be hypotonic with to rate 112 problem behaviors on a three-point scale: (0) not ligamentous hyperlaxity. He is nonverbal and expresses his true; (1) sometimes true; (2) often true. The CBCL consists needs and wants with gestures. He is shy, affectionate, and has of an internalizing domain (withdrawn, anxious/depressed, tactile defensiveness. He does not have mood instability, tem- and somatic complaints), externalizing domain (aggressive per tantrums, anxiety, or stereotypic or self-injurious behav- behavior and delinquent behavior), and three other sub- iors.Heiscurrently8yearsand11monthsoldandattends domains (social problems, thought problems, and attention 4th grade special education classes for children with severe- problems)thatsumforatotalscore[10]. The CBCL total profound intellectual disability. domain raw scores are converted to T scores. Clinically sig- The patient is the only child born to his mother and father, nificant T scores are those above 64, as established by Achen- attheagesof24yearsand27years,respectively.Hisparents bach [10] using large epidemiological samples of children. are Caucasian and not known to be consanguineous. His This patient revealed an internalizing score of 34, external- mother has dyslexia and completed the 11th grade. The patient izing scoreof44,andtotal score of 50, which indicates has three half-brothers (14, 12, and 2 years old) and one half- that he does not have maladaptive behavior, as the scores do sister (16 months old) from his parents’ previous relation- not exceed the clinical cut-off score of 64. ships. They are developing appropriately for their age except for the patient’s 2-year-old half-brother, who has develop- 3. Discussion mental delay and maladaptive behavior, which prompted testing for FXS. Subsequently, he was diagnosed with FXS We present the second known case of a boy with both DS (270–1100 CGG repeats) with complete methylation. This and full mutation FXS (Table 1). One other instance of a 14- diagnosis prompted testing for FXS in the patient at the age of year-old boy with both DS and full mutation FXS has been 8 years and 8 months. The patient’s results showed a full reported. His facial features are consistent with DS, but he mutation of the FMR1 gene (200–830 CGG repeats) with also has a prominent forehead and macroorchidism which complete