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 2 was a 53-year-old Caucasian male who had unmethylated alleles spanning from 180 to 690 CGG repeats. He had ADHD symptoms and significant impulsivity in childhood and after graduation from high school he began work as a carpenter. He developed severe hypertension at age 30 requiring antihypertensive medication. He developed an intermittent hand tremor that was noticeable when using tools or a pencil at age 49. He subsequently developed a tremor in his leg that feels as if a cell phone was vibrating in his pocket when there was none there. He experiences light-headedness and sometimes dizzy spells. On several occasions bright lights had flashed across his visual field although he did not have a history of migraines.\nOn his medical examination he had absent reflexes in all four extremities, a positive snout reflex, but no tremor nor ataxia were observed. The SCID revealed a diagnosis of Bipolar Disorder not otherwise specified (NOS) with the most current episode depressed, a history of heavy substance abuse (methamphetamine, alcohol, and stimulants), specific phobia, and a self-reported previous diagnosis ADHD with impulsivity. His MRI did not demonstrate the middle cerebellar peduncle sign which would be typical of FXTAS criteria.