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Intellectual disability, autosomal recessive 46(MRT46)

MedGen UID:
863720
Concept ID:
C4015283
Mental or Behavioral Dysfunction
Synonyms: INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 46; MRT46
 
Gene (location): NDST1 (5q33.1)
 
Monarch Initiative: MONDO:0014499
OMIM®: 616116

Definition

Any autosomal recessive non-syndromic intellectual disability in which the cause of the disease is a mutation in the NDST1 gene. [from MONDO]

Clinical features

From HPO
Pes planus
MedGen UID:
42034
Concept ID:
C0016202
Anatomical Abnormality
A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Large for gestational age
MedGen UID:
341215
Concept ID:
C1848395
Finding
The term large for gestational age applies to babies whose birth weight lies above the 90th percentile for that gestational age.
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).
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).
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).
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.
Sleep abnormality
MedGen UID:
52372
Concept ID:
C0037317
Finding
An abnormal pattern in the quality, quantity, or characteristics of sleep.
Self-injurious behavior
MedGen UID:
88371
Concept ID:
C0085271
Individual Behavior
Self-aggression.
Agitation
MedGen UID:
88447
Concept ID:
C0085631
Sign or Symptom
A state of excessive motor activity that is associated with mental distress or a feeling of substantial unease or inner tension. Distinguished from restlessness by the increased level of emotional distress and negative intensity of the experience. Agitation has a significant level of physical activity that is typically threatening to the self or others.
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.
Delayed gross motor development
MedGen UID:
332508
Concept ID:
C1837658
Finding
A type of motor delay characterized by a delay in acquiring the ability to control the large muscles of the body for walking, running, sitting, and crawling.
Poor speech
MedGen UID:
341172
Concept ID:
C1848207
Finding
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
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.
Delayed fine motor development
MedGen UID:
869257
Concept ID:
C4023681
Finding
A type of motor delay characterized by a delay in acquiring the ability to control the fingers and hands.
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.
Mandibular prognathia
MedGen UID:
98316
Concept ID:
C0399526
Finding
Abnormal prominence of the chin related to increased length of the mandible.
Epicanthus
MedGen UID:
151862
Concept ID:
C0678230
Congenital Abnormality
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).
Widely spaced teeth
MedGen UID:
337093
Concept ID:
C1844813
Finding
Increased spaces (diastemata) between most of the teeth in the same dental arch.
Synophrys
MedGen UID:
98132
Concept ID:
C0431447
Congenital Abnormality
Meeting of the medial eyebrows in the midline.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
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.

Professional guidelines

PubMed

Toktaş İ, Sarıbaş S, Canpolat S, Erdem Ö, Özbek MN
Turk J Pediatr 2022;64(6):985-992. doi: 10.24953/turkjped.2022.467. PMID: 36583880
Souza CAA, Alves MRA, Soares RDL, Kanufre VC, Rodrigues VM, Norton RC, Starling ALP, Aguiar MJB
J Pediatr (Rio J) 2018 Mar-Apr;94(2):170-176. Epub 2017 Aug 9 doi: 10.1016/j.jped.2017.04.005. PMID: 28801146
Neuhäuser G, Opitz JM
Z Kinderheilkd 1975 Nov 13;120(4):231-42. doi: 10.1007/BF00440262. PMID: 1189520

Recent clinical studies

Etiology

Toktaş İ, Sarıbaş S, Canpolat S, Erdem Ö, Özbek MN
Turk J Pediatr 2022;64(6):985-992. doi: 10.24953/turkjped.2022.467. PMID: 36583880
Ali R, Al-Dewik N, Mohammed S, Elfituri M, Agouba S, Musa S, Mahmoud L, Almulla M, El-Akouri K, Mohd H, Bux R, Almulla H, Othman A, Al-Mesaifri F, Shahbeck N, Al-Muriekhi M, Khalifa A, Al-Sulaiman R, Ben-Omran T
Am J Med Genet A 2022 Jan;188(1):116-129. Epub 2021 Sep 30 doi: 10.1002/ajmg.a.62501. PMID: 34590781
Qu R, Sang Q, Wang X, Xu Y, Chen B, Mu J, Zhang Z, Jin L, He L, Wang L
Ann Hum Genet 2020 Jan;84(1):46-53. Epub 2019 Sep 8 doi: 10.1111/ahg.12349. PMID: 31495922
Souza CAA, Alves MRA, Soares RDL, Kanufre VC, Rodrigues VM, Norton RC, Starling ALP, Aguiar MJB
J Pediatr (Rio J) 2018 Mar-Apr;94(2):170-176. Epub 2017 Aug 9 doi: 10.1016/j.jped.2017.04.005. PMID: 28801146
Bosley TM, Salih MA, Alorainy IA, Islam MZ, Oystreck DT, Suliman OS, al Malki S, Suhaibani AH, Khiari H, Beckers S, van Wesenbeeck L, Perdu B, AlDrees A, Elmalik SA, Van Hul W, Abu-Amero KK
Brain 2011 Dec;134(Pt 12):3502-15. Epub 2011 Nov 26 doi: 10.1093/brain/awr302. PMID: 22120147

Diagnosis

Toktaş İ, Sarıbaş S, Canpolat S, Erdem Ö, Özbek MN
Turk J Pediatr 2022;64(6):985-992. doi: 10.24953/turkjped.2022.467. PMID: 36583880
Manti F, Nardecchia F, Banderali G, Burlina A, Carducci C, Carducci C, Donati MA, Gueraldi D, Paci S, Pochiero F, Porta F, Ortolano R, Rovelli V, Schiaffino MC, Spada M, Blau N, Leuzzi V
Mol Genet Metab 2020 Sep-Oct;131(1-2):155-162. Epub 2020 Jun 24 doi: 10.1016/j.ymgme.2020.06.009. PMID: 32651154
Qu R, Sang Q, Wang X, Xu Y, Chen B, Mu J, Zhang Z, Jin L, He L, Wang L
Ann Hum Genet 2020 Jan;84(1):46-53. Epub 2019 Sep 8 doi: 10.1111/ahg.12349. PMID: 31495922
Reuter MS, Tawamie H, Buchert R, Hosny Gebril O, Froukh T, Thiel C, Uebe S, Ekici AB, Krumbiegel M, Zweier C, Hoyer J, Eberlein K, Bauer J, Scheller U, Strom TM, Hoffjan S, Abdelraouf ER, Meguid NA, Abboud A, Al Khateeb MA, Fakher M, Hamdan S, Ismael A, Muhammad S, Abdallah E, Sticht H, Wieczorek D, Reis A, Abou Jamra R
JAMA Psychiatry 2017 Mar 1;74(3):293-299. doi: 10.1001/jamapsychiatry.2016.3798. PMID: 28097321
Ahmed S, Jelani M, Alrayes N, Mohamoud HS, Almramhi MM, Anshasi W, Ahmed NA, Wang J, Nasir J, Al-Aama JY
J Neurol Sci 2015;353(1-2):149-54. Epub 2015 May 1 doi: 10.1016/j.jns.2015.04.038. PMID: 25956234

Therapy

Bosley TM, Salih MA, Alorainy IA, Islam MZ, Oystreck DT, Suliman OS, al Malki S, Suhaibani AH, Khiari H, Beckers S, van Wesenbeeck L, Perdu B, AlDrees A, Elmalik SA, Van Hul W, Abu-Amero KK
Brain 2011 Dec;134(Pt 12):3502-15. Epub 2011 Nov 26 doi: 10.1093/brain/awr302. PMID: 22120147
Rinat C, Zoref-Shani E, Ben-Neriah Z, Bromberg Y, Becker-Cohen R, Feinstein S, Sperling O, Frishberg Y
Mol Genet Metab 2006 Mar;87(3):249-52. Epub 2005 Dec 15 doi: 10.1016/j.ymgme.2005.09.025. PMID: 16343967
Beck J, Enders H, Schliephacke M, Buchwald-Saal M, Tümer Z
Clin Genet 1994 Oct;46(4):295-8. doi: 10.1111/j.1399-0004.1994.tb04163.x. PMID: 7834894

Prognosis

Bayat A, de Valles-Ibáñez G, Pendziwiat M, Knaus A, Alt K, Biamino E, Bley A, Calvert S, Carney P, Caro-Llopis A, Ceulemans B, Cousin J, Davis S, des Portes V, Edery P, England E, Ferreira C, Freeman J, Gener B, Gorce M, Heron D, Hildebrand MS, Jezela-Stanek A, Jouk PS, Keren B, Kloth K, Kluger G, Kuhn M, Lemke JR, Li H, Martinez F, Maxton C, Mefford HC, Merla G, Mierzewska H, Muir A, Monfort S, Nicolai J, Norman J, O'Grady G, Oleksy B, Orellana C, Orec LE, Peinhardt C, Pronicka E, Rosello M, Santos-Simarro F, Schwaibold EMC, Stegmann APA, Stumpel CT, Szczepanik E, Terczyńska I, Thevenon J, Tzschach A, Van Bogaert P, Vittorini R, Walsh S, Weckhuysen S, Weissman B, Wolfe L, Reymond A, De Nittis P, Poduri A, Olson H, Striano P, Lesca G, Scheffer IE, Møller RS, Sadleir LG
Epilepsia 2022 Apr;63(4):974-991. Epub 2022 Feb 18 doi: 10.1111/epi.17173. PMID: 35179230
Manti F, Nardecchia F, Banderali G, Burlina A, Carducci C, Carducci C, Donati MA, Gueraldi D, Paci S, Pochiero F, Porta F, Ortolano R, Rovelli V, Schiaffino MC, Spada M, Blau N, Leuzzi V
Mol Genet Metab 2020 Sep-Oct;131(1-2):155-162. Epub 2020 Jun 24 doi: 10.1016/j.ymgme.2020.06.009. PMID: 32651154
Qu R, Sang Q, Wang X, Xu Y, Chen B, Mu J, Zhang Z, Jin L, He L, Wang L
Ann Hum Genet 2020 Jan;84(1):46-53. Epub 2019 Sep 8 doi: 10.1111/ahg.12349. PMID: 31495922
Halevy A, Basel-Vanagaite L, Shuper A, Helman S, Har-Zahav A, Birk E, Maya I, Kornreich L, Inbar D, Nürnberg G, Nürnberg P, Steinberg T, Straussberg R
Pediatr Neurol 2012 Jun;46(6):363-8. doi: 10.1016/j.pediatrneurol.2012.03.014. PMID: 22633631
Bosley TM, Salih MA, Alorainy IA, Islam MZ, Oystreck DT, Suliman OS, al Malki S, Suhaibani AH, Khiari H, Beckers S, van Wesenbeeck L, Perdu B, AlDrees A, Elmalik SA, Van Hul W, Abu-Amero KK
Brain 2011 Dec;134(Pt 12):3502-15. Epub 2011 Nov 26 doi: 10.1093/brain/awr302. PMID: 22120147

Clinical prediction guides

Bayat A, de Valles-Ibáñez G, Pendziwiat M, Knaus A, Alt K, Biamino E, Bley A, Calvert S, Carney P, Caro-Llopis A, Ceulemans B, Cousin J, Davis S, des Portes V, Edery P, England E, Ferreira C, Freeman J, Gener B, Gorce M, Heron D, Hildebrand MS, Jezela-Stanek A, Jouk PS, Keren B, Kloth K, Kluger G, Kuhn M, Lemke JR, Li H, Martinez F, Maxton C, Mefford HC, Merla G, Mierzewska H, Muir A, Monfort S, Nicolai J, Norman J, O'Grady G, Oleksy B, Orellana C, Orec LE, Peinhardt C, Pronicka E, Rosello M, Santos-Simarro F, Schwaibold EMC, Stegmann APA, Stumpel CT, Szczepanik E, Terczyńska I, Thevenon J, Tzschach A, Van Bogaert P, Vittorini R, Walsh S, Weckhuysen S, Weissman B, Wolfe L, Reymond A, De Nittis P, Poduri A, Olson H, Striano P, Lesca G, Scheffer IE, Møller RS, Sadleir LG
Epilepsia 2022 Apr;63(4):974-991. Epub 2022 Feb 18 doi: 10.1111/epi.17173. PMID: 35179230
Manti F, Nardecchia F, Banderali G, Burlina A, Carducci C, Carducci C, Donati MA, Gueraldi D, Paci S, Pochiero F, Porta F, Ortolano R, Rovelli V, Schiaffino MC, Spada M, Blau N, Leuzzi V
Mol Genet Metab 2020 Sep-Oct;131(1-2):155-162. Epub 2020 Jun 24 doi: 10.1016/j.ymgme.2020.06.009. PMID: 32651154
Qu R, Sang Q, Wang X, Xu Y, Chen B, Mu J, Zhang Z, Jin L, He L, Wang L
Ann Hum Genet 2020 Jan;84(1):46-53. Epub 2019 Sep 8 doi: 10.1111/ahg.12349. PMID: 31495922
Ahmed S, Jelani M, Alrayes N, Mohamoud HS, Almramhi MM, Anshasi W, Ahmed NA, Wang J, Nasir J, Al-Aama JY
J Neurol Sci 2015;353(1-2):149-54. Epub 2015 May 1 doi: 10.1016/j.jns.2015.04.038. PMID: 25956234
Dursun U, Koroglu C, Kocasoy Orhan E, Ugur SA, Tolun A
Neurogenetics 2009 Oct;10(4):325-31. Epub 2009 May 5 doi: 10.1007/s10048-009-0191-3. PMID: 19415352

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