Table 3.

Selected Disorders of Interest in the Differential Diagnosis of HNRNPH2-Related Neurodevelopmental Disorder

Gene / Genetic MechanismDisorderMOIClinical CharacteristicsComment / Distinguishing Features
Deficient expression or function of maternally inherited UBE3A allele Angelman syndrome See footnote 1.DD/ID, speech delay, ataxic gait, & limb tremulousness; happy demeanor w/frequent smiling, laughing, & excitabilityPersons w/Angelman syndrome have more persistent regression than those w/HNRNPH2-NDD.
HNRNPH1 HNRNPH1-related syndromic ID 2ADCommon findings incl short stature, microcephaly, ID, & congenital anomalies. Dysmorphic features incl blepharophimosis, ptosis, hypotelorism, medial arched eyebrows, & micrognathia.Persons w/HNRNPH1-related syndromic ID commonly have congenital anomalies & dysmorphic features; most also have abnormalities of the cerebellar vermis on brain MRI.
MECP2 MECP2 classic Rett syndrome (See MECP2 Disorders.)XLDevelopmental regression after period of normal development; more common in females, but males have been reported; other features: slowing head growth, loss of speech, gait abnormalities, replacement of purposeful hand movements w/repetitive stereotypiesThe period of normal development (followed by developmental regression) observed in classic Rett syndrome is not seen in HNRNPH2-NDD.
PURA PURA-related neurodevelopmental disorders ADPresents w/ID & developmental & epileptic encephalopathy; characteristic neonatal features: congenital hypotonia, respiratory difficulties (most commonly due to central sleep apnea), feeding difficulties, hypersomnolence, hypothermia60% of persons w/PURA-NDD have drug-resistant epilepsy (most commonly Lennox-Gastaut syndrome); ~50% have abnormal MRI, most commonly delayed myelination & volume loss.
SLC9A6 Christianson syndrome XLIn males, DD & ID, severe speech delay, ASD or autistic behavior, hyperkinesis, epilepsy, developmental regression, truncal ataxia, acquired microcephaly, eye mvmt abnormalities, & feeding difficulties. Heterozygous females are asymptomatic or have mild ID or behavioral issues.Unlike HNRNPH2-NDD, Christianson syndrome is characteristically seen in males. Hyperkinesis is a prominent feature in affected males.

AD = autosomal dominant; ASD = autism spectrum disorder; DD = developmental delay; HNRNPH2-NDD = HNRNPH2-related neurodevelopmental disorder; ID = intellectual disability; MOI = mode of inheritance; XL = X-linked

1.

Individuals with Angelman syndrome (AS) typically represent simplex cases and have the disorder as the result of a de novo genetic alteration associated with a very low recurrence risk. Less commonly, an individual with AS has the disorder as the result of a genetic alteration associated with an imprinting pattern of autosomal dominant inheritance or variable recurrence risk.

2.

From: HNRNPH2-Related Neurodevelopmental Disorder

Cover of GeneReviews®
GeneReviews® [Internet].
Adam MP, Feldman J, Mirzaa GM, et al., editors.
Seattle (WA): University of Washington, Seattle; 1993-2024.
Copyright © 1993-2024, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2024 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.