Table 1.

Complex Genetic Neurodevelopmental Disorders with an Excessive Startle Response

GeneDisorderMOIDistinguishing Clinical FeaturesReference 1
ARHGEF9 Early-infantile epileptic encephalopathy 8XL
  • Severe ID
  • Epilepsy (often intractable focal seizures or febrile seizures)
  • Dysmorphic features
OMIM 300607
ASNS Asparagine synthetase deficiencyAR
  • Profound DD & progressive encephalopathy
  • Microcephaly
  • Hypotonia followed by spastic quadriplegia
  • Seizures
 Asparagine Synthetase Deficiency
CACNA1A Early-infantile epileptic encephalopathy 42AD
  • Epileptic encephalopathy w/myoclonic epilepsy
  • Myoclonic seizures provoked by tactile stimuli & spontaneous & reflex seizures to noise & touch
OMIM 617106
CLPB CLPB deficiency (3-methylglutaconic aciduria)AR
  • Congenital or infantile cataracts
  • Neutropenia
  • Other neurologic signs: hypotonia, spasticity, ataxia, dystonia, epilepsy, or ID
 CLPB Deficiency
CRLF1 Crisponi syndromeAR
  • Dysmorphic features, camptodactyly
  • Facial & bulbar weakness
 Cold-Induced Sweating Syndrome Including Crisponi Syndrome
CTNNB1 CTNNB1-related syndromeAD
  • Hyperekplexia is rare in this entity (single case report)
  • Later onset of hyperekplexia (not congenital but in childhood) & atypical pattern (no generalized stiffness induced by startle)
  • No congenital stiffness
  • Progressive neurologic involvement w/additional signs (ID, ataxia, spasticity)
  • Microcephaly
 CTNNB1 Neurodevelopmental Disorder
GPHN Molybdenum cofactor deficiency, complementation group CAR
  • Intractable seizures
  • Severe psychomotor retardation
  • Hypotonia combined w/hyperreflexia
  • Usually lethal in infancy
 Molybdenum Cofactor Deficiency
HEXA Tay-Sachs diseaseAR
  • DD or regression
  • Visual impairment
  • Epilepsy
  • Later: macrocephaly, decerebrate posturing, dysphagia, progression to unresponsive vegetative state
 Hexosaminidase A Deficiency
RPS6KA3 Coffin-Lowry syndromeXL
  • ID
  • Facial dysmorphism, tapering digits, & skeletal deformity
  • Besides hyperekplexia, there may be other types of stimulus-induced drop attacks (e.g., cataplexy-like episodes)
 Coffin-Lowry Syndrome
SCN8A Early-infantile epileptic encephalopathy 13ADEpileptic encephalopathy w/DD & ID SCN8A-Related Epilepsy with Encephalopathy
SLC6A9 GLYT1 encephalopathyAR
  • Hypotonia > hypertonicity
  • Arthrogryposis
  • Respiratory failure
  • Dysmorphic features
  • Encephalopathy
 GLYT1 Encephalopathy
SUOX Isolated sulfite oxidase deficiencyAR
  • Progressive epileptic encephalopathy
  • Other neurologic features: opisthotonus, spastic quadriplegia, pyramidal signs
  • Microcephaly, dysmorphic features
 Isolated Sulfite Oxidase Deficiency
TRAK1 Early-infantile epileptic encephalopathy 68AR
  • Hypotonia
  • Progressive epileptic encephalopathy
OMIM 618201
TSEN54 Pontocerebellar hypoplasia type 2AR
  • Generalized clonus ("jitteriness")
  • Delayed developmental (motor & cognitive) milestones
  • Other neurologic signs: spasticity, chorea, visual impairment, epilepsy
 TSEN54-Related Pontocerebellar Hypoplasia

AD = autosomal dominant; AR = autosomal recessive; DD = developmental delay; ID = intellectual disability; MOI = mode of inheritance; XL = X-linked

1.

OMIM phenotype entry or citation is provided if a related GeneReview is not available

From: Hereditary Hyperekplexia Overview

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.