Case 5 was a 58-year-old Caucasian male with an unmethylated full mutation. He had a long face with mildly prominent ears. He suffered from degenerative disc disease and chronic muscle pain and using an electric wheelchair. His full scale IQ of 84 fell within a low average range. On the SCID-I he met criteria for Bipolar I Disorder with a current episode of major depression. He met sub-threshold criteria for psychotic symptoms with hearing voices, and he did have some religious perseverations and grandiose thinking. He met criteria for panic disorder and generalized anxiety disorder. He had significant obsessive compulsive disorder (OCD) with sexual obsessions and frequent lock checking. On neurological examination he had an intention tremor, neuropathy symptoms, ataxia, while on physical examination he had macroorchidism (70 ml volume bilaterally) and a long face, which are features of the full mutation FXS. His MRI did not have the middle cerebellar peduncle sign but clinically, he appeared to have both FXS and FXTAS.
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.