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 14 was a 34-year-old male with a premutation of 88 CGG repeats. He had a history of ADHD and a traumatic brain injury from jumping off a bed at 5 years old. He continued to have problems in school related to impulsivity, mood lability, ADHD and learning problems. In adolescence and adulthood he developed substance abuse problems including alcohol and cocaine. He spent time in rehabilitation before being evaluated at age 34. On the SCID, he met criteria for Bipolar Disorder I with the most recent episode manic, a history of Substance Abuse, and acute stress disorder. His Verbal IQ was 112, Performance IQ was 98, and full scale IQ was 107. He suffered from intermittent intention tremor that began in his late 20 s and long-term history of balance problems. He showed some autistic features. His MRI showed some white matter disease in the insula but no middle cerebellar peduncle sign. Because of his tremor and ataxia he had a possible diagnosis of FXTAS. After evaluation he subsequently began using alcohol again in addition to cocaine and methamphetamine. He developed paranoid ideation toward his mother and his father and threatened to kill them. He was subsequently shot and killed when he attacked someone without provocation.