U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Neurodevelopmental disorder with central and peripheral motor dysfunction(NEDCPMD)

MedGen UID:
1674767
Concept ID:
C5193049
Disease or Syndrome
Synonyms: NEDCPMD; NEURODEVELOPMENTAL DISORDER WITH CENTRAL AND PERIPHERAL MOTOR DYSFUNCTION
 
Gene (location): NFASC (1q32.1)
 
Monarch Initiative: MONDO:0032698
OMIM®: 618356

Definition

Neurodevelopmental disorder with central and peripheral motor dysfunction (NEDCPMD) is an autosomal recessive neurologic disorder with a highly variable phenotype. At the severe end of the spectrum, patients may have hypotonia apparent from birth, necessitating mechanical respiration and tube-feeding, and global developmental delay with absence of reaction to touch and no eye contact. At the mild end of the spectrum, patients may present with infantile-onset progressive ataxia and demyelinating peripheral neuropathy. The disorder is caused by mutation in the NFASC gene, which has several neuronal- and glial-specific transcripts. The variable clinical phenotype may be caused by several factors, including the severity of the mutation, the selective involvement of distinct isoforms by pathogenic variants, and the presence of genetic modifiers (summary by Monfrini et al., 2019). [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.
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).
Anxiety
MedGen UID:
1613
Concept ID:
C0003467
Finding
Intense feelings of nervousness, tension, or panic often arise in response to interpersonal stresses. There is worry about the negative effects of past unpleasant experiences and future negative possibilities. Individuals may feel fearful, apprehensive, or threatened by uncertainty, and they may also have fears of falling apart or losing control.
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).
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Myoclonus
MedGen UID:
10234
Concept ID:
C0027066
Finding
Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.
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.
Dysmetria
MedGen UID:
68583
Concept ID:
C0234162
Finding
A type of ataxia characterized by the inability to carry out movements with the correct range and motion across the plane of more than one joint related to incorrect estimation of the distances required for targeted movements.
Dysdiadochokinesis
MedGen UID:
115975
Concept ID:
C0234979
Sign or Symptom
A type of ataxia characterized by the impairment of the ability to perform rapidly alternating movements, such as pronating and supinating his or her hand on the dorsum of the other hand as rapidly as possible.
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.
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.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
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.
Decreased nerve conduction velocity
MedGen UID:
347509
Concept ID:
C1857640
Finding
A reduction in the speed at which electrical signals propagate along the axon of a neuron.
Intention tremor
MedGen UID:
1642960
Concept ID:
C4551520
Sign or Symptom
A type of kinetic tremor that occurs during target directed movement is called intention tremor. That is, an oscillatory cerebellar ataxia that tends to be absent when the limbs are inactive and during the first part of voluntary movement but worsening as the movement continues and greater precision is required (e.g., in touching a target such as the patient's nose or a physician's finger).
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Hypertonia
MedGen UID:
10132
Concept ID:
C0026826
Finding
A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
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.
11 pairs of ribs
MedGen UID:
326950
Concept ID:
C1839731
Finding
Presence of only 11 pairs of ribs.
Hyperextensibility of the finger joints
MedGen UID:
334982
Concept ID:
C1844577
Finding
The ability of the finger joints to move beyond their normal range of motion.
Small anterior fontanelle
MedGen UID:
347886
Concept ID:
C1859455
Finding
Abnormally decreased size of the anterior fontanelle with respect to age-dependent norms.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Respiratory insufficiency
MedGen UID:
11197
Concept ID:
C0035229
Pathologic Function
Impairment of gas exchange within the lungs secondary to a disease process, neoplasm, or trauma, possibly resulting in hypoxia, hypercarbia, or both, but not requiring intubation or mechanical ventilation. Patients are normally managed with pharmaceutical therapy, supplemental oxygen, or both.
Congenital laryngeal stridor
MedGen UID:
78573
Concept ID:
C0265763
Congenital Abnormality
Recurrent respiratory infections
MedGen UID:
812812
Concept ID:
C3806482
Finding
An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections.
Neonatal respiratory distress
MedGen UID:
924182
Concept ID:
C4281993
Finding
Respiratory difficulty as newborn.
Glossoptosis
MedGen UID:
78623
Concept ID:
C0267048
Disease or Syndrome
Posterior displacement of the tongue into the pharynx, i.e., a tongue that is mislocalised posteriorly.
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
Prominent nasal bridge
MedGen UID:
343051
Concept ID:
C1854113
Finding
Anterior positioning of the nasal root in comparison to the usual positioning for age.
Cleft palate
MedGen UID:
756015
Concept ID:
C2981150
Congenital Abnormality
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).
Decreased fetal movement
MedGen UID:
68618
Concept ID:
C0235659
Finding
An abnormal reduction in quantity or strength of fetal movements.
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

Mroczek M, Iyadurai S
Int J Mol Sci 2023 Jan 23;24(3) doi: 10.3390/ijms24032260. PMID: 36768582Free PMC Article
Amador MDM, Masingue M, Debs R, Lamari F, Perlbarg V, Roze E, Degos B, Mochel F
J Inherit Metab Dis 2018 Sep;41(5):799-807. Epub 2018 Mar 20 doi: 10.1007/s10545-018-0162-7. PMID: 29560583
Leff AP, Behrmann M
Curr Opin Neurol 2008 Dec;21(6):644-8. doi: 10.1097/WCO.0b013e3283168dc7. PMID: 18989106

Recent clinical studies

Etiology

Frye RE, Rincon N, McCarty PJ, Brister D, Scheck AC, Rossignol DA
Neurobiol Dis 2024 Jul;197:106520. Epub 2024 May 3 doi: 10.1016/j.nbd.2024.106520. PMID: 38703861
Canton APM, Tinano FR, Guasti L, Montenegro LR, Ryan F, Shears D, de Melo ME, Gomes LG, Piana MP, Brauner R, Espino-Aguilar R, Escribano-Muñoz A, Paganoni A, Read JE, Korbonits M, Seraphim CE, Costa SS, Krepischi AC, Jorge AAL, David A, Kaisinger LR, Ong KK, Perry JRB, Abreu AP, Kaiser UB, Argente J, Mendonca BB, Brito VN, Howard SR, Latronico AC
Lancet Diabetes Endocrinol 2023 Aug;11(8):545-554. Epub 2023 Jun 26 doi: 10.1016/S2213-8587(23)00131-6. PMID: 37385287Free PMC Article
Pingault V, Zerad L, Bertani-Torres W, Bondurand N
J Med Genet 2022 Feb;59(2):105-114. Epub 2021 Oct 19 doi: 10.1136/jmedgenet-2021-108105. PMID: 34667088Free PMC Article
Walker SM
Semin Fetal Neonatal Med 2019 Aug;24(4):101005. Epub 2019 Apr 5 doi: 10.1016/j.siny.2019.04.005. PMID: 30987942
Rose SA, Wass S, Jankowski JJ, Feldman JF, Djukic A
Neuropsychology 2019 Mar;33(3):335-342. Epub 2019 Jan 28 doi: 10.1037/neu0000515. PMID: 30688490

Diagnosis

Frye RE, Rincon N, McCarty PJ, Brister D, Scheck AC, Rossignol DA
Neurobiol Dis 2024 Jul;197:106520. Epub 2024 May 3 doi: 10.1016/j.nbd.2024.106520. PMID: 38703861
Canton APM, Tinano FR, Guasti L, Montenegro LR, Ryan F, Shears D, de Melo ME, Gomes LG, Piana MP, Brauner R, Espino-Aguilar R, Escribano-Muñoz A, Paganoni A, Read JE, Korbonits M, Seraphim CE, Costa SS, Krepischi AC, Jorge AAL, David A, Kaisinger LR, Ong KK, Perry JRB, Abreu AP, Kaiser UB, Argente J, Mendonca BB, Brito VN, Howard SR, Latronico AC
Lancet Diabetes Endocrinol 2023 Aug;11(8):545-554. Epub 2023 Jun 26 doi: 10.1016/S2213-8587(23)00131-6. PMID: 37385287Free PMC Article
Lenka A, Jankovic J
Tremor Other Hyperkinet Mov (N Y) 2023;13:8. Epub 2023 Mar 28 doi: 10.5334/tohm.758. PMID: 37008994Free PMC Article
Pingault V, Zerad L, Bertani-Torres W, Bondurand N
J Med Genet 2022 Feb;59(2):105-114. Epub 2021 Oct 19 doi: 10.1136/jmedgenet-2021-108105. PMID: 34667088Free PMC Article
Kalyon S, Gökden Y, Demirel N, Erden B, Türkyılmaz A
Turk J Gastroenterol 2019 Jan;30(1):105-108. doi: 10.5152/tjg.2018.18014. PMID: 30457558Free PMC Article

Therapy

Li Y, Wang X, Yang H, Li Y, Gui J, Cui Y
Front Immunol 2022;13:843247. Epub 2022 May 26 doi: 10.3389/fimmu.2022.843247. PMID: 35693824Free PMC Article
Xiong YZ, Qiao C, Legge GE
J Vis 2019 Mar 1;19(3):17. doi: 10.1167/19.3.17. PMID: 30924845Free PMC Article
Russo R, Cristiano C, Avagliano C, De Caro C, La Rana G, Raso GM, Canani RB, Meli R, Calignano A
Curr Med Chem 2018;25(32):3930-3952. doi: 10.2174/0929867324666170216113756. PMID: 28215162
Guitart X, Codony X, Monroy X
Psychopharmacology (Berl) 2004 Jul;174(3):301-19. Epub 2004 Jun 10 doi: 10.1007/s00213-004-1920-9. PMID: 15197533
Kaufman MA, Roizin L, Gold G
Prog Neurol Psychiatry 1968;23:110-33. PMID: 4304824

Prognosis

Frye RE, Rincon N, McCarty PJ, Brister D, Scheck AC, Rossignol DA
Neurobiol Dis 2024 Jul;197:106520. Epub 2024 May 3 doi: 10.1016/j.nbd.2024.106520. PMID: 38703861
Yavas Abali Z, Gokpinar Ili E, Bas F, Ulak Ozkan M, Gulec Ç, Toksoy G, Ozturk AP, Karakilic Ozturan E, Aslanger A, Caliskan M, Yesil G, Poyrazoglu S, Darendeliler F, Oya Uyguner Z
Horm Res Paediatr 2024;97(2):157-164. Epub 2023 Jul 18 doi: 10.1159/000532000. PMID: 37463572
Lenka A, Jankovic J
Tremor Other Hyperkinet Mov (N Y) 2023;13:8. Epub 2023 Mar 28 doi: 10.5334/tohm.758. PMID: 37008994Free PMC Article
Einspieler C, Prayer D, Marschik PB
Dev Med Child Neurol 2021 Oct;63(10):1142-1148. Epub 2021 May 10 doi: 10.1111/dmcn.14918. PMID: 33973235
Latypova X, Vincent M, Mollé A, Adebambo OA, Fourgeux C, Khan TN, Caro A, Rosello M, Orellana C, Niyazov D, Lederer D, Deprez M, Capri Y, Kannu P, Tabet AC, Levy J, Aten E, den Hollander N, Splitt M, Walia J, Immken LL, Stankiewicz P, McWalter K, Suchy S, Louie RJ, Bell S, Stevenson RE, Rousseau J, Willem C, Retiere C, Yang XJ, Campeau PM, Martinez F, Rosenfeld JA, Le Caignec C, Küry S, Mercier S, Moradkhani K, Conrad S, Besnard T, Cogné B, Katsanis N, Bézieau S, Poschmann J, Davis EE, Isidor B
Am J Hum Genet 2021 May 6;108(5):929-941. Epub 2021 Apr 2 doi: 10.1016/j.ajhg.2021.03.017. PMID: 33811806Free PMC Article

Clinical prediction guides

Frye RE, Rincon N, McCarty PJ, Brister D, Scheck AC, Rossignol DA
Neurobiol Dis 2024 Jul;197:106520. Epub 2024 May 3 doi: 10.1016/j.nbd.2024.106520. PMID: 38703861
Pingault V, Zerad L, Bertani-Torres W, Bondurand N
J Med Genet 2022 Feb;59(2):105-114. Epub 2021 Oct 19 doi: 10.1136/jmedgenet-2021-108105. PMID: 34667088Free PMC Article
Einspieler C, Prayer D, Marschik PB
Dev Med Child Neurol 2021 Oct;63(10):1142-1148. Epub 2021 May 10 doi: 10.1111/dmcn.14918. PMID: 33973235
Starrfelt R, Woodhead Z
Handb Clin Neurol 2021;178:213-232. doi: 10.1016/B978-0-12-821377-3.00010-6. PMID: 33832678
Latypova X, Vincent M, Mollé A, Adebambo OA, Fourgeux C, Khan TN, Caro A, Rosello M, Orellana C, Niyazov D, Lederer D, Deprez M, Capri Y, Kannu P, Tabet AC, Levy J, Aten E, den Hollander N, Splitt M, Walia J, Immken LL, Stankiewicz P, McWalter K, Suchy S, Louie RJ, Bell S, Stevenson RE, Rousseau J, Willem C, Retiere C, Yang XJ, Campeau PM, Martinez F, Rosenfeld JA, Le Caignec C, Küry S, Mercier S, Moradkhani K, Conrad S, Besnard T, Cogné B, Katsanis N, Bézieau S, Poschmann J, Davis EE, Isidor B
Am J Hum Genet 2021 May 6;108(5):929-941. Epub 2021 Apr 2 doi: 10.1016/j.ajhg.2021.03.017. PMID: 33811806Free PMC Article

Recent systematic reviews

Frye RE, Rincon N, McCarty PJ, Brister D, Scheck AC, Rossignol DA
Neurobiol Dis 2024 Jul;197:106520. Epub 2024 May 3 doi: 10.1016/j.nbd.2024.106520. PMID: 38703861
Mroczek M, Iyadurai S
Int J Mol Sci 2023 Jan 23;24(3) doi: 10.3390/ijms24032260. PMID: 36768582Free PMC Article
Li Y, Wang X, Yang H, Li Y, Gui J, Cui Y
Front Immunol 2022;13:843247. Epub 2022 May 26 doi: 10.3389/fimmu.2022.843247. PMID: 35693824Free PMC Article
van Ierschot F, Bastiaanse R, Miceli G
Neuropsychol Rev 2018 Dec;28(4):470-495. Epub 2018 Dec 21 doi: 10.1007/s11065-018-9391-7. PMID: 30578451
Chin RY, Moran T, Fenton JE
Int J Pediatr Otorhinolaryngol 2013 May;77(5):629-34. Epub 2013 Mar 29 doi: 10.1016/j.ijporl.2013.02.006. PMID: 23541959

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Consumer resources

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...