Math exercises are visualized, and her mother promotes social skills by planning social activities regularly including outside events (theater, horseback riding) and inviting schoolmates to the home with prepared activities, encouraging phone calls with familiar people, and running errands to the supermarket independently built self-confident in socializing. At 7 years 11 months of age, with cognitive screening utilizing the Stanford-Binet, her full-scale IQ was 98, nonverbal was 87, verbal was 105, fluid reasoning is 94, knowledge is 100, quantitative reasoning is 92, visual spatial abilities 100, and working memory is 97. and hyperextensible finger joints that are the phenotype of FXS . There are the behavioral and developmental problems in child years and a variety of medications have been helpful for treating stress, aggression, AZD-0284 attention deficit hyperactivity disorders (ADHDs), and mood instability . The absence of FMRP causes impairment of synaptic plasticity  that includes upregulation of various proteins including matrix metalloproteinase 9 (MMP9) , upregulation of the metabotropic glutamate receptor 5 (mGluR5) pathway , and downregulation of the gamma-aminobutyric acid (GABA) receptors [9, 10]. The development of targeted treatments for FXS has led to trials of minocycline [11, 12], Arbaclofen  and mGluR5 antagonists [14, 15] in patients with FXS. Normal intelligence quotient (IQ) is usually uncommon AZD-0284 in males with FXS (13%) and these individuals typically have an unmethylation fully expanded gene mutation . Approximately from 30 to 50% of females with FXS can have a normal IQ [17, 18], and these individual have a favorable activation ratio and higher FMRP level . Here we present 2 cases of children with the FXS who have had a remarkable response to combined interventions and a normal IQ. 2. Case Statement Case 1 is usually a 3-year-old AZD-0284 young man carrying a full mutation allele with 245, 310, 523, 723, 1030, and 1360 CGG repeats, and 90% of his alleles are methylated. Mother had normal pregnancy and delivered full term by C-section due to preeclampsia, and he was 3700 grams at birth and suffered from torticollis and frequent emesis in the first year of life. His developmental milestones were delayed with sitting at 7-8 months, crawling at 14 months, walking independently at 18 months, and saying single terms at 2.5 years and short sentences at 3 years. He has behavior problems including severe tactile defensiveness, poor vision contact, hyperactivity, and intermittent aggression. At age 2 years and 6 months he started sertraline at 2.5?mg/day with a subsequent dramatic improvement in expressive language described as an explosion of verbalizations and the onset of phrases in speech. Minocycline (12.5?mg/day) was started two months before he turned three years, and improvement was seen in his stress and aggression. Minocycline was discontinued after 4-month treatment, resulting in the return of his behavior problems including frequent biting, chewing on his t-shirt, and an increase in his stress, so it was restarted. In conjunction with medication, he received 30 hours of physical therapy during his first year of life. After age 2 he received 1 hour of occupational therapy monthly. Now, he attends a day care program for children with special needs for 3 hours/day, 3 days per week. Additionally, his mother, who is a teacher at a vocational school, applies elements of Montessori homeschooling into Rabbit polyclonal to OMG his daily routine. The educational intervention emphasizes age-appropriate games and exercises in order to promote cognition and memory, concentration, speech, and fine and gross motor skills (e.g., singing, looking at books, applying Montessori materials, etc.). Examination at age 3 years and 2 months demonstrated normal growth percentiles, hyperextensible finger joints, and severe flat feet. On the Stanford-Binet his full-scale IQ was 94 with a nonverbal of 97 and a verbal of 92, fluid reasoning was 97, overall knowledge 111, quantitative reasoning 89, visual spatial abilities 94, and working memory 86. On the Autism Diagnostic Observation Scale (ADOS), AZD-0284 he scored in the normal range. On the Vineland Adaptive Behavior (VAB) Scales, his communication score was 85, daily living skills 91, socialization 79, and overall adaptive behavior composite 86. His motor composite on the McCarthy Scales of Children’s Ability was in the average range with a scale index of 54. Case 2 is the sister of case 1, 7 years 11 months with a full mutation allele (260C370 CGG repeats), and an activation ratio was 0.2 (only 20% of her calls have the normal X as the active X) in peripheral blood.