Clinical spectrum of KIAA2022 pathogenic variants in males: Case report of two boys with KIAA2022 pathogenic variants and review of the literature.

KIAA2022 is an X-linked intellectual disability (XLID) syndrome affecting males more severely than females. Few males with KIAA2022 variants and XLID have been reported. We present a clinical report of two unrelated males, with two nonsense KIAA2022 pathogenic variants, with profound intellectual disabilities, limited language development, strikingly similar autistic behavior, delay in motor milestones, and postnatal growth restriction. Patient 1, 19-years-old, has long ears, deeply set eyes with keratoconus, strabismus, a narrow forehead, anteverted nares, café-au-lait spots, macroglossia, thick vermilion of the upper and lower lips, and prognathism. He has gastroesophageal reflux, constipation with delayed rectosigmoid colonic transit time, difficulty regulating temperature, several musculoskeletal issues, and a history of one grand mal seizure. Patient 2, 10-years-old, has mild dysmorphic features, therapy resistant vomiting with diminished motility of the stomach, mild constipation, cortical visual impairment with intermittent strabismus, axial hypotonia, difficulty regulating temperature, and cutaneous mastocytosis. Genetic testing identified KIAA2022 variant c.652C > T(p.Arg218*) in Patient 1, and a novel nonsense de novo variant c.2707G > T(p.Glu903*) in Patient 2. We also summarized features of all reported males with KIAA2022 variants to date. This report not only adds knowledge of a novel pathogenic variant to the KIAA2022 variant database, but also likely extends the spectrum by describing novel dysmorphic features and medical conditions including macroglossia, café-au-lait spots, keratoconus, severe cutaneous mastocytosis, and motility problems of the GI tract, which may help physicians involved in the care of patients with this syndrome. Lastly, we describe the power of social media in bringing families with rare medical conditions together.

Pervasive developmental disorder, behavior problems, and psychotropic drug use in children and adolescents with mental retardation.

OBJECTIVE: This study investigated the interrelationship between psychopharmacotherapy in general and the use of specific psychotropic drugs and pervasive developmental disorder and other behavior problems in children and adolescents with mental retardation. METHODS: A total of 862 participants 4 to 18 years of age, including all levels of mental retardation, were recruited through facilities for children with mental retardation in Friesland, The Netherlands. Information on medication was collected through parent interviews. Behavior problems were investigated with a standardized parent questionnaire (Developmental Behavior Checklist). A pervasive developmental disorder classification was based on the Pervasive Developmental Disorder in Mental Retardation Scale, completed by psychologists or teachers. Logistic regression analysis was used to investigate the relationship between the use of psychotropic drugs and pervasive developmental disorder and other behavioral problems, in the presence of possible confounders. RESULTS: One of 10 participants used psychotropic medication. The main factors associated with psychotropic drug use were pervasive developmental disorder and disruptive behavior. The level of functioning was also associated. Self-absorbed behavior was statistically significantly associated with clonidine use and disruptive behavior with stimulant use. Pervasive developmental disorder and communication problems were the main factors associated with the use of antipsychotic drugs. Age also played a role, whereas gender, living situation, and level of mental retardation did not. CONCLUSIONS: Antipsychotic drugs were associated with pervasive developmental disorder, whereas clonidine and stimulants were associated with self-absorbed and disruptive behavior, respectively. Although clonidine and risperidone are not registered for the problems reported and the other nonstimulants were only sometimes used on-label, their use was associated with specific psychiatric or behavioral problems.