A Male with Cooccurrence of Down Syndrome and Fragile X Syndrome

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 not as 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 Down syndrome (DS, OMIM #190685), or trisomy 21, is the most common genetic cause of intellectual disability. Brachycephaly with flat occiput, epicanthal folds and upslanting palpebral fissures, Brushfield spots in the iris, low nasal bridge, downturned mouth with protruding tongue, low-set ears, broad neck, and small hands with transverse crease are common features in DS [1]. Since the physical gestalt is straightforward, individuals with DS are typically diagnosed in the newborn period. The physical features of Fragile X syndrome (FXS, OMIM #300684) are often subtle; hence, clinical indication is based on an array of intellectual and emotional disabilities ranging from learning problems and autism to anxiety. Families 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 behavioral phenotype commonly associated with FXS may be helpful in suggesting the diagnosis. For instance, autistic-like features, such as hand flapping, hand biting, gaze avoidance, tactile defensiveness, and hyperarousal to sensory stimuli, are common in individuals with FXS [3, 4]. Additionally, anxiety, hyperactivity, impulsivity, and aggressive behavior can also be present [5]. The cooccurrence of DS and FXS in females has been reported in two cases prior to the identification of the FMR1 gene in 1991 [7, 8]. Additionally, there has been one case report of a male with both DS and FXS [6]. Herein, we present the second case of a male with both DS and full mutation FXS, illustrating the importance of investigating additional diagnoses when a DS diagnosis does not appropriately explain the degree of