Open AccessDYRK1A pathogenic variants in two patients with syndromic intellectual disability and a review of the literature
Author(s) -
Meissner Laura E.,
Macnamara Ellen F.,
D'Souza Precilla,
Yang John,
Vezina Gilbert,
Ferreira Carlos R.,
Zein Wadih M.,
Tifft Cynthia J.,
Adams David R.
Publication year - 2020
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1544
Subject(s) - proband , intellectual disability , microcephaly , medicine , down syndrome , pediatrics , sensorineural hearing loss , audiology , hearing loss , genetics , psychiatry , biology , gene , mutation
Background DYRK1A ‐Related Intellectual Disability Syndrome is a rare autosomal dominant condition characterized by intellectual disability, speech and language delays, microcephaly, facial dysmorphism, and feeding difficulties. Affected individuals represent simplex cases that result from de novo heterozygous pathogenic variants in DYRK1A (OMIM 614104), or chromosomal structural rearrangements involving the DYRK1A locus. Due to the rarity of DYRK1A ‐Related Intellectual Disability Syndrome, the spectrum of symptoms associated with this disease has not been completely defined. Methods and results We present two unrelated cases of DYRK1A ‐Related Intellectual Disability Syndrome resulting from variants in DYRK1A . Both probands presented to the National Institutes of Health (NIH) with multiple dysmorphic facial features, primary microcephaly, absent or minimal speech, feeding difficulties, and cognitive impairment; features that have been previously reported in individuals with DYRK1A . During NIH evaluation, additional features of enlarged cerebral subarachnoid spaces, retinal vascular tortuosity, and bilateral anomalous large optic discs with increased cup‐to‐disc ratio were identified in the first proband and multiple ophthalmologic abnormalities and sensorineural hearing loss were identified in the second proband. Conclusion We recommend that the workup of future of patients include a comprehensive eye exam. Early establishment of physical, occupational, and speech therapy may help in the management of ataxia, hypertonia, and speech impairments common in these patients.