Case 1 was a 9-year-old Caucasian boy with a premutation allele of 150 that was 10% methylated. Early developmental milestones were slightly delayed and he had a history of typical FXS symptoms such as hand flapping, tactile defensiveness, hyperactivity, perseveration, recurrent otitis media, severe anxiety, and tantrums. He had severe problems with mood instability that required risperidone since age 2 and then transition to aripiprazole at age 5. Sertraline had been helpful for his severe anxiety but stimulants had not been helpful for his severe ADHD symptoms. On the WISC-IV his Verbal Comprehension was 114, but his perceptual Reasoning was 90, Working Memory was 68, and Processing Speed was 70. On physical examination he had a slightly cupped right ear, doubled jointed thumbs, flat feet, and no tremor was observed. An ADOS Module 2 assessment the age of 5 did not show any signs of an autism spectrum disorder (ASD).\nThe psychiatric interview with the K-SADS was performed with the mother and a behavioral observation of the patient. The assessment showed a significant mood regulation problem with rigidity regarding going to bed-routines, frequent awakenings, bed-wetting, and food aversions with intensive gag reflexes. He still had severe tantrum, showed signs of hyperactivity and fleeting eye-contact. On the Behavior Assessment for Children, 2nd edition he scored in the 99th percentile on the depression subscale and the externalizing problems subscale; in the 98th percentile on the hyperactivity and aggression subscale, and on the atypicality subscale including problems such as “acting strangely”, and inappropriate affect.
Case 7 was a 22-year-old Caucasian male with a full mutation with methylation mosaicism. At age 12 he showed intermittent psychotic symptoms with hearing voices in his head. At the last visit to our clinic at age 22, he had anger outbursts, attentional problems, and impulsivity and he also had a tendency to be a loner. He had some facilitated and repetitive speech, he might say “I hate you” or “I want to kill you,” which can be an automatic speech pattern typical of individuals with FXS. He showed several symptoms of an anxiety disorder and significant OCD with sexual obsessions. He had been treated with atypical antipsychotics including aripiprazole currently and risperidone in the past.