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Intellectual developmental disorder 60 with seizures(MRD60)

MedGen UID:
1684702
Concept ID:
C5231497
Disease or Syndrome
Synonyms: INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 60, WITH SEIZURES; MENTAL RETARDATION, AUTOSOMAL DOMINANT 60, WITH SEIZURES
 
Gene (location): AP2M1 (3q27.1)
 
Monarch Initiative: MONDO:0032823
OMIM®: 618587

Definition

Autosomal dominant intellectual developmental disorder-60 with seizures is characterized by global developmental delay apparent in infancy, followed by onset of seizures in the first years of life. Patients have delayed walking, an ataxic gait, and moderately to severely impaired intellectual development with poor speech (summary by Helbig et al., 2019). [from OMIM]

Clinical features

From HPO
Chorea
MedGen UID:
3420
Concept ID:
C0008489
Disease or Syndrome
Chorea (Greek for 'dance') refers to widespread arrhythmic involuntary movements of a forcible, jerky and restless fashion. It is a random-appearing sequence of one or more discrete involuntary movements or movement fragments. Movements appear random because of variability in timing, duration or location. Each movement may have a distinct start and end. However, movements may be strung together and thus may appear to flow randomly from one muscle group to another. Chorea can involve the trunk, neck, face, tongue, and extremities.
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.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Focal impaired awareness seizure
MedGen UID:
543022
Concept ID:
C0270834
Disease or Syndrome
Focal impaired awareness seizure (or focal seizure with impaired or lost awareness) is a type of focal-onset seizure characterized by some degree (which may be partial) of impairment of the person's awareness of themselves or their surroundings at any point during the seizure.
Atonic seizure
MedGen UID:
78735
Concept ID:
C0270846
Disease or Syndrome
Atonic seizure is a type of motor seizure characterized by a sudden loss or diminution of muscle tone without apparent preceding myoclonic or tonic event lasting about 1 to 2 seconds, involving head, trunk, jaw, or limb musculature.
Myoclonic-astatic epilepsy
MedGen UID:
98284
Concept ID:
C0393702
Disease or Syndrome
A generalized myoclonic-atonic seizure is a type of generalized motor seizure characterized by a myoclonic jerk followed by an atonic motor component.
Absence seizure with eyelid myoclonia
MedGen UID:
581541
Concept ID:
C0393722
Disease or Syndrome
An absence with eyelid myoclonia seizure is a type of generalized non-motor (absence) seizure characterised by forced upward jerking of the eyelids during an absence seizure.
Truncal ataxia
MedGen UID:
96535
Concept ID:
C0427190
Sign or Symptom
Truncal ataxia is a sign of ataxia characterized by instability of the trunk. It usually occurs during sitting.
Bilateral tonic-clonic seizure
MedGen UID:
141670
Concept ID:
C0494475
Sign or Symptom
A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase.
Atypical absence seizure
MedGen UID:
108888
Concept ID:
C0595948
Disease or Syndrome
An atypical absence seizure is a type of generalised non-motor (absence) seizure characterised by interruption of ongoing activities and reduced responsiveness. In comparison to a typical absence seizure, changes in tone may be more pronounced, onset and/or cessation may be less abrupt, and the duration of the ictus and post-ictal recovery may be longer. Although not always available, an EEG often demonstrates slow (<3 Hz), irregular, generalized spike-wave activity.
Gait ataxia
MedGen UID:
155642
Concept ID:
C0751837
Sign or Symptom
A type of ataxia characterized by the impairment of the ability to coordinate the movements required for normal walking. Gait ataxia is characteirzed by a wide-based staggering gait with a tendency to fall.
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.
Abnormal cerebral white matter morphology
MedGen UID:
181756
Concept ID:
C0948163
Pathologic Function
An abnormality of the cerebral white matter.
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.
EEG with polyspike wave complexes
MedGen UID:
867392
Concept ID:
C4021757
Finding
The presence of complexes of repetitive spikes and waves in EEG.
EEG with spike-wave complexes
MedGen UID:
869259
Concept ID:
C4023683
Finding
Complexes of spikes (<70 ms) and sharp waves (70-200 ms), which are sharp transient waves that have a strong association with epilepsy, in cerebral electrical activity recorded along the scalp by electroencephalography (EEG).
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Hyperplasia of the maxilla
MedGen UID:
892487
Concept ID:
C2227090
Finding
Abnormally increased dimension of the maxilla, especially relative to the mandible, resulting in a malocclusion or malalignment between the upper and lower teeth or in anterior positioning of the nasal base, increased convexity of the face, increased nasolabial angle, or increased width (transverse dimension of the maxilla.
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).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Martinez-Cayuelas E, Blanco-Kelly F, Lopez-Grondona F, Swafiri ST, Lopez-Rodriguez R, Losada-Del Pozo R, Mahillo-Fernandez I, Moreno B, Rodrigo-Moreno M, Casas-Alba D, Lopez-Gonzalez A, García-Miñaúr S, Ángeles Mori M, Pacio-Minguez M, Rikeros-Orozco E, Santos-Simarro F, Cruz-Rojo J, Quesada-Espinosa JF, Sanchez-Calvin MT, Sanchez-Del Pozo J, Bernado Fonz R, Isidoro-Garcia M, Ruiz-Ayucar I, Alvarez-Mora MI, Blanco-Lago R, De Azua B, Eiris J, Garcia-Peñas JJ, Gil-Fournier B, Gomez-Lado C, Irazabal N, Lopez-Gonzalez V, Madrigal I, Malaga I, Martinez-Menendez B, Ramiro-Leon S, Garcia-Hoyos M, Prieto-Matos P, Lopez-Pison J, Aguilera-Albesa S, Alvarez S, Fernández-Jaén A, Llano-Rivas I, Gener-Querol B, Ayuso C, Arteche-Lopez A, Palomares-Bralo M, Cueto-González A, Valenzuela I, Martinez-Monseny A, Lorda-Sanchez I, Almoguera B
J Med Genet 2023 Jul;60(7):644-654. Epub 2022 Nov 29 doi: 10.1136/jmg-2022-108632. PMID: 36446582
Hart K, Rohrwasser A, Wallis H, Golsan H, Shao J, Anderson T, Wang X, Szabo-Fresnais N, Morrissey M, Kay DM, Wojcik M, Galvin-Parton PA, Longo N, Caggana M, Pasquali M
Mol Genet Metab 2021 Sep-Oct;134(1-2):60-64. Epub 2021 Jul 29 doi: 10.1016/j.ymgme.2021.07.012. PMID: 34389248
Wolff M, Brunklaus A, Zuberi SM
Epilepsia 2019 Dec;60 Suppl 3:S59-S67. doi: 10.1111/epi.14935. PMID: 31904126

Recent clinical studies

Etiology

Lennard S, Henley W, McLean B, Allard J, Parrett M, Jadav M, Laugharne R, Shankar R
J Neurol 2022 Jul;269(7):3770-3778. Epub 2022 Feb 13 doi: 10.1007/s00415-022-11006-0. PMID: 35152336
Brunklaus A, Pérez-Palma E, Ghanty I, Xinge J, Brilstra E, Ceulemans B, Chemaly N, de Lange I, Depienne C, Guerrini R, Mei D, Møller RS, Nabbout R, Regan BM, Schneider AL, Scheffer IE, Schoonjans AS, Symonds JD, Weckhuysen S, Kattan MW, Zuberi SM, Lal D
Neurology 2022 Mar 15;98(11):e1163-e1174. Epub 2022 Jan 24 doi: 10.1212/WNL.0000000000200028. PMID: 35074891Free PMC Article
Hedrich UBS, Lauxmann S, Lerche H
Epilepsia 2019 Dec;60 Suppl 3:S68-S76. doi: 10.1111/epi.14731. PMID: 31904120
Strasser L, Downes M, Kung J, Cross JH, De Haan M
Dev Med Child Neurol 2018 Jan;60(1):19-29. Epub 2017 Nov 9 doi: 10.1111/dmcn.13598. PMID: 29119560
Cox DM, Butler MG
Int J Mol Sci 2015 Feb 13;16(2):4068-82. doi: 10.3390/ijms16024068. PMID: 25689425Free PMC Article

Diagnosis

Lennard S, Henley W, McLean B, Allard J, Parrett M, Jadav M, Laugharne R, Shankar R
J Neurol 2022 Jul;269(7):3770-3778. Epub 2022 Feb 13 doi: 10.1007/s00415-022-11006-0. PMID: 35152336
Brunklaus A, Pérez-Palma E, Ghanty I, Xinge J, Brilstra E, Ceulemans B, Chemaly N, de Lange I, Depienne C, Guerrini R, Mei D, Møller RS, Nabbout R, Regan BM, Schneider AL, Scheffer IE, Schoonjans AS, Symonds JD, Weckhuysen S, Kattan MW, Zuberi SM, Lal D
Neurology 2022 Mar 15;98(11):e1163-e1174. Epub 2022 Jan 24 doi: 10.1212/WNL.0000000000200028. PMID: 35074891Free PMC Article
Scheffer IE, Nabbout R
Epilepsia 2019 Dec;60 Suppl 3:S17-S24. doi: 10.1111/epi.16386. PMID: 31904117
Arends JBAM
Epilepsia 2018 Jun;59 Suppl 1:30-35. Epub 2018 Apr 9 doi: 10.1111/epi.14053. PMID: 29635767
Zis P, Strydom A
Free Radic Biol Med 2018 Jan;114:3-9. Epub 2017 Sep 1 doi: 10.1016/j.freeradbiomed.2017.08.024. PMID: 28870521Free PMC Article

Therapy

Coughlin CR, Tseng LA, Bok LA, Hartmann H, Footitt E, Striano P, Tabarki BM, Lunsing RJ, Stockler-Ipsiroglu S, Gordon S, Van Hove JLK, Abdenur JE, Boyer M, Longo N, Andrews A, Janssen MCH, van Wegberg A, Prasad C, Prasad AN, Lamb MM, Wijburg FA, Gospe SM Jr, van Karnebeek C; International PDE Consortium
Neurology 2022 Dec 5;99(23):e2627-e2636. doi: 10.1212/WNL.0000000000201222. PMID: 36008148Free PMC Article
Harvey S, Allen NM, King MD, Lynch B, Lynch SA, O'Regan M, O'Rourke D, Shahwan A, Webb D, Gorman KM; Irish Paediatric Neurology Group
Dev Med Child Neurol 2022 Jun;64(6):780-788. Epub 2022 Jan 29 doi: 10.1111/dmcn.15153. PMID: 35092693Free PMC Article
Fobian AD, Long DM, Szaflarski JP
Ann Clin Transl Neurol 2020 Aug;7(8):1410-1419. Epub 2020 Aug 3 doi: 10.1002/acn3.51138. PMID: 32748572Free PMC Article
Wolff M, Brunklaus A, Zuberi SM
Epilepsia 2019 Dec;60 Suppl 3:S59-S67. doi: 10.1111/epi.14935. PMID: 31904126
Arends JBAM
Epilepsia 2018 Jun;59 Suppl 1:30-35. Epub 2018 Apr 9 doi: 10.1111/epi.14053. PMID: 29635767

Prognosis

Brunklaus A, Pérez-Palma E, Ghanty I, Xinge J, Brilstra E, Ceulemans B, Chemaly N, de Lange I, Depienne C, Guerrini R, Mei D, Møller RS, Nabbout R, Regan BM, Schneider AL, Scheffer IE, Schoonjans AS, Symonds JD, Weckhuysen S, Kattan MW, Zuberi SM, Lal D
Neurology 2022 Mar 15;98(11):e1163-e1174. Epub 2022 Jan 24 doi: 10.1212/WNL.0000000000200028. PMID: 35074891Free PMC Article
Poke G, King C, Muir A, de Valles-Ibáñez G, Germano M, Moura de Souza CF, Fung J, Chung B, Fung CW, Mignot C, Ilea A, Keren B, Vermersch AI, Davis S, Stanley T, Moharir M, Kannu P, Shao Z, Malerba N, Merla G, Mefford HC, Scheffer IE, Sadleir LG
Epilepsia 2019 Nov;60(11):e121-e127. Epub 2019 Oct 20 doi: 10.1111/epi.16372. PMID: 31631344
Kleist A, Kerling F, Hamer H, Winterholler M
Acta Neurol Belg 2019 Sep;119(3):423-430. Epub 2019 Mar 6 doi: 10.1007/s13760-019-01098-3. PMID: 30840220
Arends JBAM
Epilepsia 2018 Jun;59 Suppl 1:30-35. Epub 2018 Apr 9 doi: 10.1111/epi.14053. PMID: 29635767
Camfield PR, Camfield CS
Pediatr Neurol 2014 Jul;51(1):17-23. Epub 2014 Mar 4 doi: 10.1016/j.pediatrneurol.2014.02.020. PMID: 24830766

Clinical prediction guides

Coughlin CR, Tseng LA, Bok LA, Hartmann H, Footitt E, Striano P, Tabarki BM, Lunsing RJ, Stockler-Ipsiroglu S, Gordon S, Van Hove JLK, Abdenur JE, Boyer M, Longo N, Andrews A, Janssen MCH, van Wegberg A, Prasad C, Prasad AN, Lamb MM, Wijburg FA, Gospe SM Jr, van Karnebeek C; International PDE Consortium
Neurology 2022 Dec 5;99(23):e2627-e2636. doi: 10.1212/WNL.0000000000201222. PMID: 36008148Free PMC Article
Brunklaus A, Pérez-Palma E, Ghanty I, Xinge J, Brilstra E, Ceulemans B, Chemaly N, de Lange I, Depienne C, Guerrini R, Mei D, Møller RS, Nabbout R, Regan BM, Schneider AL, Scheffer IE, Schoonjans AS, Symonds JD, Weckhuysen S, Kattan MW, Zuberi SM, Lal D
Neurology 2022 Mar 15;98(11):e1163-e1174. Epub 2022 Jan 24 doi: 10.1212/WNL.0000000000200028. PMID: 35074891Free PMC Article
Carvill GL, Jansen S, Lacroix A, Zemel M, Mehaffey M, De Vries P, Brunner HG, Scheffer IE, De Vries BBA, Vissers LELM, Mefford HC
Dev Med Child Neurol 2021 Dec;63(12):1441-1447. Epub 2021 Jul 11 doi: 10.1111/dmcn.14989. PMID: 34247411
Arends JBAM
Epilepsia 2018 Jun;59 Suppl 1:30-35. Epub 2018 Apr 9 doi: 10.1111/epi.14053. PMID: 29635767
Cox DM, Butler MG
Int J Mol Sci 2015 Feb 13;16(2):4068-82. doi: 10.3390/ijms16024068. PMID: 25689425Free PMC Article

Recent systematic reviews

Schigt H, Bald M, van der Eerden BCJ, Gal L, Ilenwabor BP, Konrad M, Levine MA, Li D, Mache CJ, Mackin S, Perry C, Rios FJ, Schlingmann KP, Storey B, Trapp CM, Verkerk AJMH, Zillikens MC, Touyz RM, Hoorn EJ, Hoenderop JGJ, de Baaij JHF
J Clin Endocrinol Metab 2023 Aug 18;108(9):e754-e768. doi: 10.1210/clinem/dgad147. PMID: 36916904Free PMC Article
Strasser L, Downes M, Kung J, Cross JH, De Haan M
Dev Med Child Neurol 2018 Jan;60(1):19-29. Epub 2017 Nov 9 doi: 10.1111/dmcn.13598. PMID: 29119560
van Ool JS, Snoeijen-Schouwenaars FM, Schelhaas HJ, Tan IY, Aldenkamp AP, Hendriksen JGM
Epilepsy Behav 2016 Jul;60:130-137. Epub 2016 May 18 doi: 10.1016/j.yebeh.2016.04.018. PMID: 27206231
van Karnebeek CD, Shevell M, Zschocke J, Moeschler JB, Stockler S
Mol Genet Metab 2014 Apr;111(4):428-38. Epub 2014 Jan 24 doi: 10.1016/j.ymgme.2014.01.011. PMID: 24518794
van Karnebeek CD, Stockler S
Mol Genet Metab 2012 Mar;105(3):368-81. Epub 2011 Nov 30 doi: 10.1016/j.ymgme.2011.11.191. PMID: 22212131

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