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Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction(NEDCAM)

MedGen UID:
1781936
Concept ID:
C5543427
Disease or Syndrome
Synonyms: NEDCAM; NEURODEVELOPMENTAL DISORDER WITH CEREBELLAR ATROPHY AND MOTOR DYSFUNCTION
 
Gene (location): GEMIN5 (5q33.2)
 
Monarch Initiative: MONDO:0859152
OMIM®: 619333

Definition

Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction (NEDCAM) is an autosomal recessive disorder characterized by global developmental delay with prominent motor abnormalities, mainly axial hypotonia, gait ataxia, and appendicular spasticity. Affected individuals have cognitive impairment and speech delay; brain imaging shows cerebellar atrophy. The severity is variable (summary by Kour et al., 2021). [from OMIM]

Clinical features

From HPO
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
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.
Inability to walk
MedGen UID:
107860
Concept ID:
C0560046
Finding
Incapability to ambulate.
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Brisk reflexes
MedGen UID:
382164
Concept ID:
C2673700
Finding
Tendon reflexes that are noticeably more active than usual (conventionally denoted 3+ on clinical examination). Brisk reflexes may or may not indicate a neurological lesion. They are distinguished from hyperreflexia by the fact that hyerreflexia is characterized by hyperactive repeating (clonic) reflexes, which are considered to be always abnormal.
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.
Appendicular hypotonia
MedGen UID:
868520
Concept ID:
C4022919
Finding
Muscular hypotonia of one or more limbs.

Professional guidelines

PubMed

Nuovo S, Baglioni V, De Mori R, Tardivo S, Caputi C, Ginevrino M, Micalizzi A, Masuelli L, Federici G, Casella A, Lorefice E, Anello D, Tolve M, Farini D, Bertini E, Zanni G, Travaglini L, Vasco G, Sette C, Carducci C, Valente EM, Leuzzi V
Hum Mutat 2022 Jan;43(1):67-73. Epub 2021 Nov 15 doi: 10.1002/humu.24293. PMID: 34747546
Méreaux JL, Firanescu C, Coarelli G, Kvarnung M, Rodrigues R, Pegoraro E, Tazir M, Taithe F, Valter R, Huin V, Lidström K, Banneau G, Morais S, Parodi L, Coutelier M, Papin M, Svenningsson P, Azulay JP, Alonso I, Nilsson D, Brice A, Le Guern E, Press R, Vazza G, Loureiro JL, Goizet C, Durr A, Paucar M, Stevanin G
Neurogenetics 2021 Mar;22(1):71-79. Epub 2021 Jan 23 doi: 10.1007/s10048-020-00633-2. PMID: 33486633Free PMC Article
Kjaergaard S, Schwartz M, Skovby F
Arch Dis Child 2001 Sep;85(3):236-9. doi: 10.1136/adc.85.3.236. PMID: 11517108Free PMC Article

Recent clinical studies

Etiology

Tremblay M, Girard-Côté L, Brais B, Gagnon C
Orphanet J Rare Dis 2022 Oct 1;17(1):369. doi: 10.1186/s13023-022-02497-1. PMID: 36183078Free PMC Article
Santos M, Damásio J, Carmona S, Neto JL, Dehghani N, Guedes LC, Barbot C, Barros J, Brás J, Sequeiros J, Guerreiro R
Cells 2022 Mar 12;11(6) doi: 10.3390/cells11060981. PMID: 35326432Free PMC Article
Nicita F, Ginevrino M, Travaglini L, D'Arrigo S, Zorzi G, Borgatti R, Terrone G, Catteruccia M, Vasco G, Brankovic V, Siliquini S, Romano S, Veredice C, Pedemonte M, Armando M, Lettori D, Stregapede F, Bosco L, Sferra A, Tessarollo V, Romaniello R, Ristori G, Bertini E, Valente EM, Zanni G
J Med Genet 2021 Jul;58(7):475-483. Epub 2020 Jul 31 doi: 10.1136/jmedgenet-2020-107007. PMID: 32737135
Indelicato E, Nachbauer W, Fauth C, Krabichler B, Schossig A, Eigentler A, Dichtl W, Wenning G, Wagner M, Fanciulli A, Janecke A, Boesch S
Parkinsonism Relat Disord 2019 May;62:210-214. Epub 2018 Dec 11 doi: 10.1016/j.parkreldis.2018.12.007. PMID: 30573412
Uccelli A, Gattorno M
Clin Exp Rheumatol 2018 Jan-Feb;36 Suppl 110(1):61-67. Epub 2018 May 3 PMID: 29742058

Diagnosis

Karaer K, Karaer D, Yüksel Z, Işikay S
Clin Dysmorphol 2022 Oct 1;31(4):167-173. Epub 2022 Jul 14 doi: 10.1097/MCD.0000000000000426. PMID: 36004946
Romaniello R, Pasca L, Panzeri E, D'Abrusco F, Travaglini L, Serpieri V, Signorini S, Aiello C, Bertini E, Bassi MT, Valente EM, Zanni G, Borgatti R, Arrigoni F
Int J Mol Sci 2022 Jun 16;23(12) doi: 10.3390/ijms23126723. PMID: 35743164Free PMC Article
Pedroso JL, Vale TC, França Junior MC, Kauffman MA, Teive H, Barsottini OGP, Munhoz RP
Cerebellum 2022 Dec;21(6):1073-1084. Epub 2021 Nov 15 doi: 10.1007/s12311-021-01345-5. PMID: 34782953
Bereznyakova O, Dupré N
Handb Clin Neurol 2018;155:191-203. doi: 10.1016/B978-0-444-64189-2.00012-3. PMID: 29891058
Vassar RL, Rose J
Handb Clin Neurol 2014;125:237-51. doi: 10.1016/B978-0-444-62619-6.00015-X. PMID: 25307579

Therapy

Squire LR, Kim S, Frascino JC, Annese J, Bennett J, Insausti R, Amaral DG
Proc Natl Acad Sci U S A 2020 Nov 24;117(47):29883-29893. Epub 2020 Nov 9 doi: 10.1073/pnas.2018960117. PMID: 33168712Free PMC Article
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
Gagnon C, Brais B, Lessard I, Lavoie C, Côté I, Mathieu J
Orphanet J Rare Dis 2018 Sep 19;13(1):165. doi: 10.1186/s13023-018-0898-z. PMID: 30231904Free PMC Article
Buderath P, Gärtner K, Frings M, Christiansen H, Schoch B, Konczak J, Gizewski ER, Hebebrand J, Timmann D
Gait Posture 2009 Feb;29(2):249-54. Epub 2008 Oct 28 doi: 10.1016/j.gaitpost.2008.08.016. PMID: 18963991
Tajima T, Fujiwara F, Sudo A, Saito S, Fujieda K
Endocr J 2007 Dec;54(6):941-4. Epub 2007 Nov 14 doi: 10.1507/endocrj.k07-105. PMID: 18000345

Prognosis

Velasco HM, Ullah E, Martin AM, Hufnagel RB, Prada CE
Am J Med Genet A 2020 Oct;182(10):2214-2221. Epub 2020 Aug 11 doi: 10.1002/ajmg.a.61782. PMID: 32783359Free PMC Article
Chelban V, Alsagob M, Kloth K, Chirita-Emandi A, Vandrovcova J, Maroofian R, Davagnanam I, Bakhtiari S, AlSayed MD, Rahbeeni Z, AlZaidan H, Malintan NT, Johannsen J, Efthymiou S, Ghayoor Karimiani E, Mankad K, Al-Shahrani SA, Beiraghi Toosi M, AlShammari M, Groppa S, Haridy NA, AlQuait L, Qari A, Huma R, Salih MA, Almass R, Almutairi FB, Hamad MH, Alorainy IA, Ramzan K, Imtiaz F, Puiu M, Kruer MC, Bierhals T, Wood NW, Colak D, Houlden H, Kaya N
Eur J Neurol 2020 Feb;27(2):334-342. Epub 2019 Oct 17 doi: 10.1111/ene.14082. PMID: 31509304Free PMC Article
Indelicato E, Nachbauer W, Fauth C, Krabichler B, Schossig A, Eigentler A, Dichtl W, Wenning G, Wagner M, Fanciulli A, Janecke A, Boesch S
Parkinsonism Relat Disord 2019 May;62:210-214. Epub 2018 Dec 11 doi: 10.1016/j.parkreldis.2018.12.007. PMID: 30573412
Meuwissen ME, Mancini GM
Eur J Med Genet 2012 May;55(5):323-31. Epub 2012 May 4 doi: 10.1016/j.ejmg.2012.04.007. PMID: 22564885
Steinlin M
Cerebellum 2008;7(4):607-10. Epub 2008 Dec 5 doi: 10.1007/s12311-008-0083-3. PMID: 19057977

Clinical prediction guides

Majethia P, Do Rosario MC, Kaur P, Karanvir, Shankar R, Sharma S, Siddiqui S, Shukla A
Ann Hum Genet 2022 Mar;86(2):94-101. Epub 2021 Dec 8 doi: 10.1111/ahg.12452. PMID: 34878169Free PMC Article
Kessi M, Chen B, Peng J, Yan F, Yang L, Yin F
Orphanet J Rare Dis 2021 May 13;16(1):219. doi: 10.1186/s13023-021-01850-0. PMID: 33985586Free PMC Article
Zhang MJ, Cao YX, Wu HY, Li HH
Brain Behav 2021 May;11(5):e02079. Epub 2021 Mar 18 doi: 10.1002/brb3.2079. PMID: 33734615Free PMC Article
Sakaguchi Y, Yoshihashi H, Uehara T, Miyama S, Kosaki K, Takenouchi T
Am J Med Genet A 2021 Mar;185(3):884-888. Epub 2020 Dec 27 doi: 10.1002/ajmg.a.62020. PMID: 33369122
Buderath P, Gärtner K, Frings M, Christiansen H, Schoch B, Konczak J, Gizewski ER, Hebebrand J, Timmann D
Gait Posture 2009 Feb;29(2):249-54. Epub 2008 Oct 28 doi: 10.1016/j.gaitpost.2008.08.016. PMID: 18963991

Recent systematic reviews

Kessi M, Chen B, Peng J, Yan F, Yang L, Yin F
Orphanet J Rare Dis 2021 May 13;16(1):219. doi: 10.1186/s13023-021-01850-0. PMID: 33985586Free PMC Article

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