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 3 was a 36-year-old Caucasian male with a full mutation with methylation mosaicism. He was adopted at birth, and his birth mother had a history of drugs and alcohol. He reached his developmental milestones delayed (walking at 15 months, speaking single words at 18 months, phrase speech at age 5½ years). Upon medical examination, he demonstrated a long, somewhat narrow face. His palate was high-arched. His ears pinnae were not prominent but they were long measuring 7 cm in length. He was diagnosed with atypical autism at 5-years of age and had a history of ADHD problems. At the time of puberty he became more aggressive and his anxiety increased. According to the caregiver, he had two psychotic breaks at age 29 and 31 and was subsequently diagnosed with schizophrenia. He had been treated with aripiprazole and clonidine.