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Severe intellectual disability-progressive spastic diplegia syndrome(NEDSDV)

MedGen UID:
767363
Concept ID:
C3554449
Disease or Syndrome
Synonyms: NEDSDV; NEURODEVELOPMENTAL DISORDER WITH SPASTIC DIPLEGIA AND VISUAL DEFECTS
Modes of inheritance:
Unknown inheritance
MedGen UID:
989040
Concept ID:
CN307042
Finding
Source: Orphanet
Hereditary clinical entity whose mode of inheritance is unknown.
 
Gene (location): CTNNB1 (3p22.1)
 
Monarch Initiative: MONDO:0014035
OMIM®: 615075
Orphanet: ORPHA404473

Disease characteristics

Excerpted from the GeneReview: CTNNB1 Neurodevelopmental Disorder
CTNNB1 neurodevelopmental disorder (CTNNB1-NDD) is characterized in all individuals by mild-to-profound cognitive impairment and in up to 39% of reported individuals by exudative vitreoretinopathy, an ophthalmologic finding consistent with familial exudative vitreoretinopathy (FEVR). Other common findings include truncal hypotonia, peripheral spasticity, dystonia, behavior problems, microcephaly, and refractive errors and strabismus. Less common features include intrauterine growth restriction, feeding difficulties, and scoliosis. [from GeneReviews]
Authors:
Stephanie KL Ho  |  Mandy HY Tsang  |  Mianne Lee, et. al.   view full author information

Additional description

From OMIM
Neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV) is characterized by global developmental delay, impaired intellectual development, axial hypotonia, and dysmorphic craniofacial features with microcephaly. Many patients have visual abnormalities, ranging from strabismus to optic nerve atrophy and retinal abnormalities. Affected individuals also develop spasticity, particularly of the lower limbs, and may have behavioral abnormalities (summary by Kuechler et al., 2015 and Kharbanda et al., 2017).  http://www.omim.org/entry/615075

Clinical features

From HPO
Broad finger
MedGen UID:
375540
Concept ID:
C1844906
Finding
Increased width of a non-thumb digit of the hand.
Small for gestational age
MedGen UID:
65920
Concept ID:
C0235991
Finding
Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age.
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Feeding difficulties
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Aggressive behavior
MedGen UID:
1375
Concept ID:
C0001807
Individual Behavior
Behavior or an act aimed at harming a person, animal, or physical property (e.g., acts of physical violence; shouting, swearing, and using harsh language; slashing someone's tires).
Spastic diplegia
MedGen UID:
44181
Concept ID:
C0023882
Disease or Syndrome
Spasticity (neuromuscular hypertonia) primarily in the muscles of the legs, hips, and pelvis.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Self-mutilation
MedGen UID:
19925
Concept ID:
C0036601
Injury or Poisoning
Deliberate harm to one's body resulting in tissue damage, without a conscious intent to die.
Delayed ability to walk
MedGen UID:
66034
Concept ID:
C0241726
Finding
A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Autistic behavior
MedGen UID:
163547
Concept ID:
C0856975
Mental or Behavioral Dysfunction
Persistent deficits in social interaction and communication and interaction as well as a markedly restricted repertoire of activity and interest as well as repetitive patterns of behavior.
Progressive spasticity
MedGen UID:
347171
Concept ID:
C1859520
Finding
Spasticity that increases in degree with time.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Restlessness
MedGen UID:
854457
Concept ID:
C3887611
Sign or Symptom
A state of unease is characterized by diffuse motor activity or motion, which is subject to limited control, nonproductive, or disorganized behavior.
Delayed ability to sit
MedGen UID:
1368737
Concept ID:
C4476710
Finding
A failure to achieve the ability to sit at an appropriate developmental stage. Most children sit with support at 6 months of age and sit steadily without support at 9 months of age.
Delayed ability to crawl
MedGen UID:
1772845
Concept ID:
C5421628
Finding
A failure to achieve the ability to crawl at an appropriate developmental stage. Normal infant motor development is marked by a series of postural milestones including learning to crawl on hands and knees between the ages of 6 and 10 months.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Primary microcephaly
MedGen UID:
383046
Concept ID:
C2677180
Finding
Head circumference below 2 standard deviations below the mean for age and gender at birth.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Broad nasal tip
MedGen UID:
98424
Concept ID:
C0426429
Finding
Increase in width of the nasal tip.
Long philtrum
MedGen UID:
351278
Concept ID:
C1865014
Finding
Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border.
Thin upper lip vermilion
MedGen UID:
355352
Concept ID:
C1865017
Finding
Height of the vermilion of the upper lip in the midline more than 2 SD below the mean. Alternatively, an apparently reduced height of the vermilion of the upper lip in the frontal view (subjective).
Hypermetropia
MedGen UID:
43780
Concept ID:
C0020490
Disease or Syndrome
An abnormality of refraction characterized by the ability to see objects in the distance clearly, while objects nearby appear blurry.
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.
Exudative vitreoretinopathy
MedGen UID:
892913
Concept ID:
C4072980
Disease or Syndrome

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVSevere intellectual disability-progressive spastic diplegia syndrome
Follow this link to review classifications for Severe intellectual disability-progressive spastic diplegia syndrome in Orphanet.

Professional guidelines

PubMed

Bin Sawad A, Jackimiec J, Bechter M, Trucillo A, Lindsley K, Bhagat A, Uyei J, Diaz GA
Mol Genet Metab 2022 Sep-Oct;137(1-2):153-163. Epub 2022 Aug 25 doi: 10.1016/j.ymgme.2022.08.005. PMID: 36049366
Hauer J, Houtrow AJ; SECTION ON HOSPICE AND PALLIATIVE MEDICINE, COUNCIL ON CHILDREN WITH DISABILITIES
Pediatrics 2017 Jun;139(6) doi: 10.1542/peds.2017-1002. PMID: 28562301
O'Shea TM
Clin Obstet Gynecol 2008 Dec;51(4):816-28. doi: 10.1097/GRF.0b013e3181870ba7. PMID: 18981805Free PMC Article

Recent clinical studies

Etiology

Ristovska S, Stomnaroska O, Danilovski D
Pril (Makedon Akad Nauk Umet Odd Med Nauki) 2022 Apr 22;43(1):77-84. doi: 10.2478/prilozi-2022-0013. PMID: 35451288
Ostrander B, Bale JF
Handb Clin Neurol 2019;162:133-153. doi: 10.1016/B978-0-444-64029-1.00006-0. PMID: 31324308
Rogers EE, Hintz SR
Semin Perinatol 2016 Dec;40(8):497-509. Epub 2016 Nov 16 doi: 10.1053/j.semperi.2016.09.002. PMID: 27865437
Colver A, Fairhurst C, Pharoah PO
Lancet 2014 Apr 5;383(9924):1240-9. Epub 2013 Nov 20 doi: 10.1016/S0140-6736(13)61835-8. PMID: 24268104
O'Shea TM
Clin Obstet Gynecol 2008 Dec;51(4):816-28. doi: 10.1097/GRF.0b013e3181870ba7. PMID: 18981805Free PMC Article

Diagnosis

Ristovska S, Stomnaroska O, Danilovski D
Pril (Makedon Akad Nauk Umet Odd Med Nauki) 2022 Apr 22;43(1):77-84. doi: 10.2478/prilozi-2022-0013. PMID: 35451288
Ostrander B, Bale JF
Handb Clin Neurol 2019;162:133-153. doi: 10.1016/B978-0-444-64029-1.00006-0. PMID: 31324308
Colver A, Fairhurst C, Pharoah PO
Lancet 2014 Apr 5;383(9924):1240-9. Epub 2013 Nov 20 doi: 10.1016/S0140-6736(13)61835-8. PMID: 24268104
des Portes V
Handb Clin Neurol 2013;111:297-306. doi: 10.1016/B978-0-444-52891-9.00035-X. PMID: 23622180
O'Shea TM
Clin Obstet Gynecol 2008 Dec;51(4):816-28. doi: 10.1097/GRF.0b013e3181870ba7. PMID: 18981805Free PMC Article

Therapy

Matsuda T, Akezaki Y, Tsuji Y, Hamada K, Ookura M
Acta Med Okayama 2022 Oct;76(5):535-540. doi: 10.18926/AMO/64034. PMID: 36352800
Bin Sawad A, Jackimiec J, Bechter M, Trucillo A, Lindsley K, Bhagat A, Uyei J, Diaz GA
Mol Genet Metab 2022 Sep-Oct;137(1-2):153-163. Epub 2022 Aug 25 doi: 10.1016/j.ymgme.2022.08.005. PMID: 36049366
Harvey AR, Baker LB, Reddihough DS, Scheinberg A, Williams K
Cochrane Database Syst Rev 2018 May 15;5(5):CD012430. doi: 10.1002/14651858.CD012430.pub2. PMID: 29763510Free PMC Article
McAdams RM, Juul SE
Clin Perinatol 2016 Sep;43(3):485-500. Epub 2016 Jun 22 doi: 10.1016/j.clp.2016.04.007. PMID: 27524449Free PMC Article
Colver A, Fairhurst C, Pharoah PO
Lancet 2014 Apr 5;383(9924):1240-9. Epub 2013 Nov 20 doi: 10.1016/S0140-6736(13)61835-8. PMID: 24268104

Prognosis

Alpay Savasan Z, Kim SK, Oh KJ, Graham SF
Adv Clin Chem 2021;100:139-169. Epub 2020 May 23 doi: 10.1016/bs.acc.2020.04.006. PMID: 33453864
Cho KH, Shim SH, Kim M
Clin Genet 2018 Apr;93(4):721-730. Epub 2017 Sep 17 doi: 10.1111/cge.13058. PMID: 28543186
Rogers EE, Hintz SR
Semin Perinatol 2016 Dec;40(8):497-509. Epub 2016 Nov 16 doi: 10.1053/j.semperi.2016.09.002. PMID: 27865437
Colver A, Fairhurst C, Pharoah PO
Lancet 2014 Apr 5;383(9924):1240-9. Epub 2013 Nov 20 doi: 10.1016/S0140-6736(13)61835-8. PMID: 24268104
O'Shea TM
Clin Obstet Gynecol 2008 Dec;51(4):816-28. doi: 10.1097/GRF.0b013e3181870ba7. PMID: 18981805Free PMC Article

Clinical prediction guides

Mo A, Saffari A, Kellner M, Döbler-Neumann M, Jordan C, Srivastava S, Zhang B, Sahin M, Fink JK, Smith L, Posey JE, Alter KE, Toro C, Blackstone C, Soldatos AG, Christie M, Schüle R, Ebrahimi-Fakhari D
Mov Disord 2022 Dec;37(12):2440-2446. Epub 2022 Sep 14 doi: 10.1002/mds.29225. PMID: 36103453Free PMC Article
Alpay Savasan Z, Kim SK, Oh KJ, Graham SF
Adv Clin Chem 2021;100:139-169. Epub 2020 May 23 doi: 10.1016/bs.acc.2020.04.006. PMID: 33453864
Scherer N, Verhey I, Kuper H
PLoS One 2019;14(7):e0219888. Epub 2019 Jul 30 doi: 10.1371/journal.pone.0219888. PMID: 31361768Free PMC Article
Pisani F, Spagnoli C
Handb Clin Neurol 2019;162:401-414. doi: 10.1016/B978-0-444-64029-1.00019-9. PMID: 31324322
O'Shea TM
Clin Obstet Gynecol 2008 Dec;51(4):816-28. doi: 10.1097/GRF.0b013e3181870ba7. PMID: 18981805Free PMC Article

Recent systematic reviews

Bin Sawad A, Jackimiec J, Bechter M, Trucillo A, Lindsley K, Bhagat A, Uyei J, Diaz GA
Mol Genet Metab 2022 Sep-Oct;137(1-2):153-163. Epub 2022 Aug 25 doi: 10.1016/j.ymgme.2022.08.005. PMID: 36049366
Scherer N, Verhey I, Kuper H
PLoS One 2019;14(7):e0219888. Epub 2019 Jul 30 doi: 10.1371/journal.pone.0219888. PMID: 31361768Free PMC Article
Coenen MA, Eggink H, Tijssen MA, Spikman JM
Dev Med Child Neurol 2018 Mar;60(3):244-255. Epub 2017 Dec 14 doi: 10.1111/dmcn.13632. PMID: 29238959
Robertson J, Chadwick D, Baines S, Emerson E, Hatton C
Intellect Dev Disabil 2017 Dec;55(6):377-391. doi: 10.1352/1934-9556-55.6.377. PMID: 29194030
Hielkema T, Hadders-Algra M
Dev Med Child Neurol 2016 Mar;58 Suppl 4:46-52. doi: 10.1111/dmcn.13047. PMID: 27027607

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