Van Bon et al. (2011) reported a woman with primary microcephaly (-3 SD), severe mental retardation without speech, anxious autistic behavior, and dysmorphic features, including bitemporal narrowing, deep-set eyes, large simple ears, and a pointed nasal tip. As ... Van Bon et al. (2011) reported a woman with primary microcephaly (-3 SD), severe mental retardation without speech, anxious autistic behavior, and dysmorphic features, including bitemporal narrowing, deep-set eyes, large simple ears, and a pointed nasal tip. As an infant, she had failure to thrive, abnormal movements, hypoactivity, and febrile seizures. Brain MRI at age 25 showed a mildly atrophic brain without structural abnormalities. Other features included eczema, hypoplasia of breasts, hallux valgus of feet, and an irregular implant of the toes. Van Bon et al. (2011) noted that their patient clearly resembled the 2 patients reported by Moller et al. (2008). Courcet et al. (2012) reported a 14-year-old girl with severe mental retardation, primary microcephaly (-6 SD), and facial dysmorphic features, including thick lower lip, mild hypotelorism, and hypoplastic earlobes. She had a history of intrauterine growth retardation and feeding difficulties, and developed seizures of multiple types at age 18 months. Other features included severe speech delay, diffuse cortical atrophy on MRI, and hand stereotypies.
In a woman with mental retardation, microcephaly, and dysmorphic features, van Bon et al. (2011) identified a de novo heterozygous deletion in the DYRK1A gene (600855.0001). This patient was identified among a larger group of 3,009 mentally retarded ... In a woman with mental retardation, microcephaly, and dysmorphic features, van Bon et al. (2011) identified a de novo heterozygous deletion in the DYRK1A gene (600855.0001). This patient was identified among a larger group of 3,009 mentally retarded individuals studied for copy number variations in the DYRK1A gene. The report supported a role for DYRK1A in human brain development and showed that haploinsufficiency of DYRK1A can cause a distinctive clinical syndrome with mental retardation, primary microcephaly, intrauterine growth retardation, facial dysmorphism, impaired motor functioning, and behavioral problems. O'Roak et al. (2012) identified 3 de novo mutations in DYRK1A, 2 frameshift mutations and 1 splice site mutation (600855.0002-600855.0004), among 44 candidate gene sequences in 2,446 autism spectrum disorder probands. The 3 patients with DYRK1A mutations had microcephaly relative to individuals screened without DYRK1A mutations (2-sample permutation test, 2-sided p = 0.0005), and the head sizes of these patients was smaller than those of their parents. In a 14-year-old girl with severe mental retardation, growth retardation, microcephaly, speech delay, and seizures, Courcet et al. (2012) identified a de novo heterozygous truncating mutation in the DYRK1A gene (600855.0005). This patient was ascertained from a larger cohort of 150 patients with a similar phenotype; she was the only one who had a mutation in the DYRK1A gene.