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Neurodevelopmental disorder with spasticity, seizures, and brain abnormalities(NEDSSBA)

MedGen UID:
1823970
Concept ID:
C5774197
Disease or Syndrome
Synonym: NEDSSBA
 
Gene (location): NSRP1 (17q11.2)
 
Monarch Initiative: MONDO:0859275
OMIM®: 620001

Definition

Neurodevelopmental disorder with spasticity, seizures, and brain abnormalities (NEDSSBA) is an autosomal recessive disorder characterized by global developmental delay apparent in infancy, axial hypotonia, peripheral spasticity, and early-onset seizures of various types and severity. Affected individuals have delayed walking or are unable to walk and show impaired intellectual development with poor or absent speech. Brain imaging may show developmental defects of the operculum, cerebellum, and corpus callosum. Death in early childhood may occur (Calame et al., 2021). [from OMIM]

Clinical features

From HPO
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Posteriorly rotated ears
MedGen UID:
96566
Concept ID:
C0431478
Congenital Abnormality
A type of abnormal location of the ears in which the position of the ears is characterized by posterior rotation (the superior part of the ears is rotated towards the back of the head, and the inferior part of the ears towards the front).
Simple ear
MedGen UID:
140913
Concept ID:
C0431483
Congenital Abnormality
The pinna has fewer folds and grooves than usual.
Protruding ear
MedGen UID:
343309
Concept ID:
C1855285
Finding
Angle formed by the plane of the ear and the mastoid bone greater than the 97th centile for age (objective); or, outer edge of the helix more than 2 cm from the mastoid at the point of maximum distance (objective).
Cerebral palsy
MedGen UID:
854
Concept ID:
C0007789
Disease or Syndrome
Cerebral palsy describes a group of permanent disorders of the development of movement and posture, causing activity limitation, that are attributed to nonprogressive disturbances that occurred in the developing fetal or infant brain. The motor disorders of cerebral palsy are often accompanied by disturbances of sensation, perception, cognition, communication, and behavior, by epilepsy, and by secondary musculoskeletal problems.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Dysplastic corpus callosum
MedGen UID:
98128
Concept ID:
C0431369
Congenital Abnormality
Dysplasia and dysgenesis of the corpus callosum are nonspecific descriptions that imply defective development of the corpus callosum. The term dysplasia is applied when the morphology of the corpus callosum is altered as a congenital trait. For instance, the corpus callosum may be hump-shaped, kinked, or a striped corpus callosum that lacks an anatomically distinct genu and splenium.
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.
Persistent head lag
MedGen UID:
256151
Concept ID:
C1141883
Finding
The Premie-Neuro and the Dubowitz Neurological Examination score head lag in the same manner. Scoring for both is as follows
Cerebellar vermis hypoplasia
MedGen UID:
333548
Concept ID:
C1840379
Finding
Underdevelopment of the vermis of cerebellum.
Hypoplasia of the brainstem
MedGen UID:
334226
Concept ID:
C1842688
Finding
Underdevelopment of the brainstem.
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
Simplified gyral pattern
MedGen UID:
413664
Concept ID:
C2749675
Finding
An abnormality of the cerebral cortex with fewer gyri but with normal cortical thickness. This pattern is usually often associated with congenital microcephaly.
Interictal epileptiform activity
MedGen UID:
869073
Concept ID:
C4023491
Finding
Epileptiform activity refers to distinctive EEG waves or complexes distinguished from background activity found in in a proportion of human subjects with epilepsy, but which can also be found in subjects without seizures. Interictal epileptiform activity refers to such activity that occurs in the absence of a clinical or subclinical seizure.
Appendicular spasticity
MedGen UID:
937224
Concept ID:
C4313257
Finding
A type of spasticity that affects one or more limbs (arms or legs).
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Axial hypotonia
MedGen UID:
342959
Concept ID:
C1853743
Finding
Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk.
Prominent metopic ridge
MedGen UID:
387953
Concept ID:
C1857949
Finding
Vertical bony ridge positioned in the midline of the forehead.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
High forehead
MedGen UID:
65991
Concept ID:
C0239676
Finding
An abnormally increased height of the forehead.
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).
Mandibular prognathia
MedGen UID:
98316
Concept ID:
C0399526
Finding
Abnormal prominence of the chin related to increased length of the mandible.
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Tented upper lip vermilion
MedGen UID:
326574
Concept ID:
C1839767
Finding
Triangular appearance of the oral aperture with the apex in the midpoint of the upper vermilion and the lower vermilion forming the base.
Anteverted nares
MedGen UID:
326648
Concept ID:
C1840077
Finding
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
Short philtrum
MedGen UID:
350006
Concept ID:
C1861324
Finding
Distance between nasal base and midline upper lip vermilion border more than 2 SD below the mean. Alternatively, an apparently decreased distance between nasal base and midline upper lip vermilion border.
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.
Sparse hair
MedGen UID:
1790211
Concept ID:
C5551005
Finding
Reduced density of hairs.
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).

Professional guidelines

PubMed

Sudnawa KK, Li W, Calamia S, Kanner CH, Bain JM, Abdelhakim AH, Geltzeiler A, Mebane CM, Provenzano FA, Sands TT, Fee RJ, Montes J, Shen Y, Chung WK
Genet Med 2024 Aug;26(8):101169. Epub 2024 May 21 doi: 10.1016/j.gim.2024.101169. PMID: 38785164Free PMC Article
Almannai M, Marafi D, Abdel-Salam GMH, Zaki MS, Duan R, Calame D, Herman I, Levesque F, Elbendary HM, Hegazy I, Chung WK, Kavus H, Saeidi K, Maroofian R, AlHashim A, Al-Otaibi A, Al Madhi A, Abou Al-Seood HM, Alasmari A, Houlden H, Gleeson JG, Hunter JV, Posey JE, Lupski JR, El-Hattab AW
Clin Genet 2022 May;101(5-6):530-540. Epub 2022 Apr 12 doi: 10.1111/cge.14132. PMID: 35322404Free PMC Article
Trinh J, Imhoff S, Dulovic-Mahlow M, Kandaswamy KK, Tadic V, Schäfer J, Dobricic V, Nolte A, Werber M, Rolfs A, Münchau A, Klein C, Lohmann K, Brüggemann N
J Neurol 2020 Mar;267(3):770-782. Epub 2019 Nov 20 doi: 10.1007/s00415-019-09640-2. PMID: 31745726

Recent clinical studies

Etiology

Ivarola P, Urdinez L, Oleastro M, Labonia D, Roizen M, Caraballo R, Tenembaum S
Pediatr Neurol 2024 Sep;158:49-56. Epub 2024 Jun 8 doi: 10.1016/j.pediatrneurol.2024.05.022. PMID: 38959649
Sudnawa KK, Li W, Calamia S, Kanner CH, Bain JM, Abdelhakim AH, Geltzeiler A, Mebane CM, Provenzano FA, Sands TT, Fee RJ, Montes J, Shen Y, Chung WK
Genet Med 2024 Aug;26(8):101169. Epub 2024 May 21 doi: 10.1016/j.gim.2024.101169. PMID: 38785164Free PMC Article
Pérez IF, Villagra TB, Jiménez-Balado J, Redondo JJ, Recasens BB
Epilepsy Behav 2023 Oct;147:109450. Epub 2023 Sep 26 doi: 10.1016/j.yebeh.2023.109450. PMID: 37769423
Alharby E, Faqeih EA, Saleh M, Alameer S, Almuntashri M, Pastore A, Samman MA, Alnawfal AM, Hashem M, Zaytuni D, Alharbi G, Almannai M, Alasmari A, Mahmoud AA, Alwadei AH, Jad L, AlOtaibi A, Al-Hakami F, Eyaid W, Alkuraya FS, Alfadhel M, Peake RWA, Almontashiri NAM
Genet Med 2020 Dec;22(12):2071-2080. Epub 2020 Aug 3 doi: 10.1038/s41436-020-0919-x. PMID: 32741967
Sherr EH
Curr Opin Pediatr 2003 Dec;15(6):567-71. doi: 10.1097/00008480-200312000-00004. PMID: 14631200

Diagnosis

Ivarola P, Urdinez L, Oleastro M, Labonia D, Roizen M, Caraballo R, Tenembaum S
Pediatr Neurol 2024 Sep;158:49-56. Epub 2024 Jun 8 doi: 10.1016/j.pediatrneurol.2024.05.022. PMID: 38959649
Efthymiou S, Scala M, Nagaraj V, Ochenkowska K, Komdeur FL, Liang RA, Abdel-Hamid MS, Sultan T, Barøy T, Van Ghelue M, Vona B, Maroofian R, Zafar F, Alkuraya FS, Zaki MS, Severino M, Duru KC, Tryon RC, Brauteset LV, Ansari M, Hamilton M, van Haelst MM, van Haaften G, Zara F, Houlden H, Samarut É, Nichols CG, Smeland MF, McClenaghan C
Brain 2024 May 3;147(5):1822-1836. doi: 10.1093/brain/awae010. PMID: 38217872Free PMC Article
Pérez IF, Villagra TB, Jiménez-Balado J, Redondo JJ, Recasens BB
Epilepsy Behav 2023 Oct;147:109450. Epub 2023 Sep 26 doi: 10.1016/j.yebeh.2023.109450. PMID: 37769423
Fattal-Valevski A, Ben Sira L, Lerman-Sagie T, Strausberg R, Bloch-Mimouni A, Edvardson S, Kaufman R, Chernuha V, Schneebaum Sender N, Heimer G, Ben Zeev B
Eur J Paediatr Neurol 2021 May;32:40-45. Epub 2021 Mar 5 doi: 10.1016/j.ejpn.2020.08.011. PMID: 33756211
Pearson TS, Akman C, Hinton VJ, Engelstad K, De Vivo DC
Curr Neurol Neurosci Rep 2013 Apr;13(4):342. doi: 10.1007/s11910-013-0342-7. PMID: 23443458

Therapy

Boets S, Johannesen KM, Destree A, Manti F, Ramantani G, Lesca G, Vercueil L, Koenig MK, Striano P, Møller RS, Cooper E, Weckhuysen S
J Med Genet 2022 Jun;59(6):528-535. Epub 2021 Apr 2 doi: 10.1136/jmedgenet-2020-107449. PMID: 33811133
Trinh J, Imhoff S, Dulovic-Mahlow M, Kandaswamy KK, Tadic V, Schäfer J, Dobricic V, Nolte A, Werber M, Rolfs A, Münchau A, Klein C, Lohmann K, Brüggemann N
J Neurol 2020 Mar;267(3):770-782. Epub 2019 Nov 20 doi: 10.1007/s00415-019-09640-2. PMID: 31745726
Fichera M, Failla P, Saccuzzo L, Miceli M, Salvo E, Castiglia L, Galesi O, Grillo L, Calì F, Greco D, Amato C, Romano C, Elia M
Hum Genet 2019 Feb;138(2):187-198. Epub 2019 Jan 17 doi: 10.1007/s00439-019-01972-3. PMID: 30656450
Pearson TS, Akman C, Hinton VJ, Engelstad K, De Vivo DC
Curr Neurol Neurosci Rep 2013 Apr;13(4):342. doi: 10.1007/s11910-013-0342-7. PMID: 23443458
Lewis AJ, Simon EM, Barkovich AJ, Clegg NJ, Delgado MR, Levey E, Hahn JS
Neurology 2002 Dec 24;59(12):1860-5. doi: 10.1212/01.wnl.0000037483.31989.b9. PMID: 12499474

Prognosis

Sudnawa KK, Li W, Calamia S, Kanner CH, Bain JM, Abdelhakim AH, Geltzeiler A, Mebane CM, Provenzano FA, Sands TT, Fee RJ, Montes J, Shen Y, Chung WK
Genet Med 2024 Aug;26(8):101169. Epub 2024 May 21 doi: 10.1016/j.gim.2024.101169. PMID: 38785164Free PMC Article
Efthymiou S, Scala M, Nagaraj V, Ochenkowska K, Komdeur FL, Liang RA, Abdel-Hamid MS, Sultan T, Barøy T, Van Ghelue M, Vona B, Maroofian R, Zafar F, Alkuraya FS, Zaki MS, Severino M, Duru KC, Tryon RC, Brauteset LV, Ansari M, Hamilton M, van Haelst MM, van Haaften G, Zara F, Houlden H, Samarut É, Nichols CG, Smeland MF, McClenaghan C
Brain 2024 May 3;147(5):1822-1836. doi: 10.1093/brain/awae010. PMID: 38217872Free PMC Article
Boets S, Johannesen KM, Destree A, Manti F, Ramantani G, Lesca G, Vercueil L, Koenig MK, Striano P, Møller RS, Cooper E, Weckhuysen S
J Med Genet 2022 Jun;59(6):528-535. Epub 2021 Apr 2 doi: 10.1136/jmedgenet-2020-107449. PMID: 33811133
Himes RW, Chiou EH, Queliza K, Shouval DS, Somech R, Agarwal S, Jajoo K, Ziegler DS, Kratz CP, Huang J, Lucas TL, Myers KC, Nelson AS, DiNardo CD, Alter BP, Giri N, Khincha PP, McReynolds LJ, Dufour C, Pierri F, Goldman FD, Sherif Y, Savage SA, Miloh T, Bertuch AA
J Pediatr 2021 Mar;230:55-61.e4. Epub 2020 Sep 21 doi: 10.1016/j.jpeds.2020.09.038. PMID: 32971146
Alharby E, Faqeih EA, Saleh M, Alameer S, Almuntashri M, Pastore A, Samman MA, Alnawfal AM, Hashem M, Zaytuni D, Alharbi G, Almannai M, Alasmari A, Mahmoud AA, Alwadei AH, Jad L, AlOtaibi A, Al-Hakami F, Eyaid W, Alkuraya FS, Alfadhel M, Peake RWA, Almontashiri NAM
Genet Med 2020 Dec;22(12):2071-2080. Epub 2020 Aug 3 doi: 10.1038/s41436-020-0919-x. PMID: 32741967

Clinical prediction guides

Ivarola P, Urdinez L, Oleastro M, Labonia D, Roizen M, Caraballo R, Tenembaum S
Pediatr Neurol 2024 Sep;158:49-56. Epub 2024 Jun 8 doi: 10.1016/j.pediatrneurol.2024.05.022. PMID: 38959649
Sudnawa KK, Li W, Calamia S, Kanner CH, Bain JM, Abdelhakim AH, Geltzeiler A, Mebane CM, Provenzano FA, Sands TT, Fee RJ, Montes J, Shen Y, Chung WK
Genet Med 2024 Aug;26(8):101169. Epub 2024 May 21 doi: 10.1016/j.gim.2024.101169. PMID: 38785164Free PMC Article
Efthymiou S, Scala M, Nagaraj V, Ochenkowska K, Komdeur FL, Liang RA, Abdel-Hamid MS, Sultan T, Barøy T, Van Ghelue M, Vona B, Maroofian R, Zafar F, Alkuraya FS, Zaki MS, Severino M, Duru KC, Tryon RC, Brauteset LV, Ansari M, Hamilton M, van Haelst MM, van Haaften G, Zara F, Houlden H, Samarut É, Nichols CG, Smeland MF, McClenaghan C
Brain 2024 May 3;147(5):1822-1836. doi: 10.1093/brain/awae010. PMID: 38217872Free PMC Article
Kaiyrzhanov R, Rad A, Lin SJ, Bertoli-Avella A, Kallemeijn WW, Godwin A, Zaki MS, Huang K, Lau T, Petree C, Efthymiou S, Karimiani EG, Hempel M, Normand EA, Rudnik-Schöneborn S, Schatz UA, Baggelaar MP, Ilyas M, Sultan T, Alvi JR, Ganieva M, Fowler B, Aanicai R, Tayfun GA, Al Saman A, Alswaid A, Amiri N, Asilova N, Shotelersuk V, Yeetong P, Azam M, Babaei M, Monajemi GB, Mohammadi P, Samie S, Banu SH, Pinto Basto J, Kortüm F, Bauer M, Bauer P, Beetz C, Garshasbi M, Issa AH, Eyaid W, Ahmed H, Hashemi N, Hassanpour K, Herman I, Ibrohimov S, Abdul-Majeed BA, Imdad M, Isrofilov M, Kaiyal Q, Khan S, Kirmse B, Koster J, Lourenço CM, Mitani T, Moldovan O, Murphy D, Najafi M, Pehlivan D, Rocha ME, Salpietro V, Schmidts M, Shalata A, Mahroum M, Talbeya JK, Taylor RW, Vazquez D, Vetro A, Waterham HR, Zaman M, Schrader TA, Chung WK, Guerrini R, Lupski JR, Gleeson J, Suri M, Jamshidi Y, Bhatia KP, Vona B, Schrader M, Severino M, Guille M, Tate EW, Varshney GK, Houlden H, Maroofian R
Brain 2024 Apr 4;147(4):1436-1456. doi: 10.1093/brain/awad380. PMID: 37951597Free PMC Article
Kopyta I, Jamroz E, Kluczewska E, Sarecka-Hujar B
J Child Neurol 2014 Apr;29(4):442-9. Epub 2013 Mar 14 doi: 10.1177/0883073813478660. PMID: 23503883

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