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Intellectual developmental disorder 59(MRD59)

MedGen UID:
1678593
Concept ID:
C5193190
Disease or Syndrome
Synonyms: INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 59; MENTAL RETARDATION, AUTOSOMAL DOMINANT 59
 
Gene (location): CAMK2G (10q22.2)
 
Monarch Initiative: MONDO:0032795
OMIM®: 618522

Clinical features

From HPO
Brachydactyly
MedGen UID:
67454
Concept ID:
C0221357
Congenital Abnormality
Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.
Short palm
MedGen UID:
334684
Concept ID:
C1843108
Finding
Short palm.
Short foot
MedGen UID:
376415
Concept ID:
C1848673
Finding
A measured foot length that is more than 2 SD below the mean for a newborn of 27 - 41 weeks gestation, or foot that is less than the 3rd centile for individuals from birth to 16 years of age (objective). Alternatively, a foot that appears disproportionately short (subjective).
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).
Mild short stature
MedGen UID:
461427
Concept ID:
C3150077
Finding
A mild degree of short stature, more than -2 SD but not more than -3 SD from mean corrected for age and sex.
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.
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).
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.
Self-mutilation
MedGen UID:
19925
Concept ID:
C0036601
Injury or Poisoning
Deliberate harm to one's body resulting in tissue damage, without a conscious intent to die.
Intellectual disability, severe
MedGen UID:
48638
Concept ID:
C0036857
Mental or Behavioral Dysfunction
Severe mental retardation is defined as an intelligence quotient (IQ) in the range of 20-34.
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.
Poor speech
MedGen UID:
341172
Concept ID:
C1848207
Finding
Facial hypotonia
MedGen UID:
336889
Concept ID:
C1845251
Finding
Reduced muscle tone of a muscle that is innervated by the facial nerve (the seventh cranial nerve).
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.
High forehead
MedGen UID:
65991
Concept ID:
C0239676
Finding
An abnormally increased height of the forehead.
Narrow forehead
MedGen UID:
326956
Concept ID:
C1839758
Finding
Width of the forehead or distance between the frontotemporales is more than two standard deviations below the mean (objective); or apparently narrow intertemporal region (subjective).
Long palpebral fissure
MedGen UID:
340300
Concept ID:
C1849340
Finding
Distance between medial and lateral canthi is more than two standard deviations above the mean for age (objective); or, apparently increased length of the palpebral fissures.
Flat face
MedGen UID:
342829
Concept ID:
C1853241
Finding
Absence of concavity or convexity of the face when viewed in profile.
Flat forehead
MedGen UID:
347463
Concept ID:
C1857485
Finding
A forehead with abnormal flatness.
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.
Highly arched eyebrow
MedGen UID:
358357
Concept ID:
C1868571
Finding
Increased height of the central portion of the eyebrow, forming a crescent, semicircular, or inverted U shape.
Sacral dimple
MedGen UID:
98428
Concept ID:
C0426848
Finding
A cutaneous indentation resulting from tethering of the skin to underlying structures (bone) of the intergluteal cleft.
Fragile nails
MedGen UID:
341661
Concept ID:
C1856963
Finding
Nails that easily break.
Myopia
MedGen UID:
44558
Concept ID:
C0027092
Disease or Syndrome
Nearsightedness, also known as myopia, is an eye condition that causes blurry distance vision. People who are nearsighted have more trouble seeing things that are far away (such as when driving) than things that are close up (such as when reading or using a computer). If it is not treated with corrective lenses or surgery, nearsightedness can lead to squinting, eyestrain, headaches, and significant visual impairment.\n\nNearsightedness usually begins in childhood or adolescence. It tends to worsen with age until adulthood, when it may stop getting worse (stabilize). In some people, nearsightedness improves in later adulthood.\n\nFor normal vision, light passes through the clear cornea at the front of the eye and is focused by the lens onto the surface of the retina, which is the lining of the back of the eye that contains light-sensing cells. People who are nearsighted typically have eyeballs that are too long from front to back. As a result, light entering the eye is focused too far forward, in front of the retina instead of on its surface. It is this change that causes distant objects to appear blurry. The longer the eyeball is, the farther forward light rays will be focused and the more severely nearsighted a person will be.\n\nNearsightedness is measured by how powerful a lens must be to correct it. The standard unit of lens power is called a diopter. Negative (minus) powered lenses are used to correct nearsightedness. The more severe a person's nearsightedness, the larger the number of diopters required for correction. In an individual with nearsightedness, one eye may be more nearsighted than the other.\n\nEye doctors often refer to nearsightedness less than -5 or -6 diopters as "common myopia." Nearsightedness of -6 diopters or more is commonly called "high myopia." This distinction is important because high myopia increases a person's risk of developing other eye problems that can lead to permanent vision loss or blindness. These problems include tearing and detachment of the retina, clouding of the lens (cataract), and an eye disease called glaucoma that is usually related to increased pressure within the eye. The risk of these other eye problems increases with the severity of the nearsightedness. The term "pathological myopia" is used to describe cases in which high myopia leads to tissue damage within the eye.
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

Kessi M, Chen B, Shan LD, Wang Y, Yang L, Yin F, He F, Peng J, Wang G
BMC Med Genomics 2023 Mar 7;16(1):46. doi: 10.1186/s12920-023-01474-2. PMID: 36882827Free PMC Article
Gavril EC, Nucă I, Pânzaru MC, Ivanov AV, Mihai CT, Antoci LM, Ciobanu CG, Rusu C, Popescu R
Genes (Basel) 2023 Feb 11;14(2) doi: 10.3390/genes14020465. PMID: 36833393Free PMC Article
Juneja M, Gupta A, Sairam S, Jain R, Sharma M, Thadani A, Srinivasan R, Lingappa L, Ahmed S, Multani KS, Buch P, Chatterjee N, Dalwai S, Kabra M, Kapoor S, Patel PK, Girisha KM, Kulkarni M, Kunju PAM, Malhi P, Meenai Z, Mishra D, Mundkur N, Nair MKC, Oommen SP, Prasad C, Singh A, Srivastava L, Suman P, Thakur R
Indian Pediatr 2022 May 15;59(5):401-415. Epub 2022 Feb 19 PMID: 35188106

Recent clinical studies

Etiology

Maenner MJ, Warren Z, Williams AR, Amoakohene E, Bakian AV, Bilder DA, Durkin MS, Fitzgerald RT, Furnier SM, Hughes MM, Ladd-Acosta CM, McArthur D, Pas ET, Salinas A, Vehorn A, Williams S, Esler A, Grzybowski A, Hall-Lande J, Nguyen RHN, Pierce K, Zahorodny W, Hudson A, Hallas L, Mancilla KC, Patrick M, Shenouda J, Sidwell K, DiRienzo M, Gutierrez J, Spivey MH, Lopez M, Pettygrove S, Schwenk YD, Washington A, Shaw KA
MMWR Surveill Summ 2023 Mar 24;72(2):1-14. doi: 10.15585/mmwr.ss7202a1. PMID: 36952288Free PMC Article
Denommé-Pichon AS, Matalonga L, de Boer E, Jackson A, Benetti E, Banka S, Bruel AL, Ciolfi A, Clayton-Smith J, Dallapiccola B, Duffourd Y, Ellwanger K, Fallerini C, Gilissen C, Graessner H, Haack TB, Havlovicova M, Hoischen A, Jean-Marçais N, Kleefstra T, López-Martín E, Macek M, Mencarelli MA, Moutton S, Pfundt R, Pizzi S, Posada M, Radio FC, Renieri A, Rooryck C, Ryba L, Safraou H, Schwarz M, Tartaglia M, Thauvin-Robinet C, Thevenon J, Tran Mau-Them F, Trimouille A, Votypka P, de Vries BBA, Willemsen MH, Zurek B, Verloes A, Philippe C; Solve-RD DITF-ITHACA; Solve-RD SNV-indel Working Group; Solve-RD Consortia; Orphanomix Group, Vitobello A, Vissers LELM, Faivre L
Genet Med 2023 Apr;25(4):100018. Epub 2023 Jan 20 doi: 10.1016/j.gim.2023.100018. PMID: 36681873
Van Biesen D, Van Damme T, Pineda RC, Burns J
J Intellect Disabil 2023 Mar;27(1):104-120. Epub 2022 Feb 18 doi: 10.1177/17446295211036331. PMID: 35176890
Dalsgaard S, Thorsteinsson E, Trabjerg BB, Schullehner J, Plana-Ripoll O, Brikell I, Wimberley T, Thygesen M, Madsen KB, Timmerman A, Schendel D, McGrath JJ, Mortensen PB, Pedersen CB
JAMA Psychiatry 2020 Feb 1;77(2):155-164. doi: 10.1001/jamapsychiatry.2019.3523. PMID: 31746968Free PMC Article
Witmer C, Mattingly A, DʼSouza P, Thurm A, Hadigan C
J Pediatr Gastroenterol Nutr 2019 Aug;69(2):e39-e42. doi: 10.1097/MPG.0000000000002342. PMID: 30921255Free PMC Article

Diagnosis

Maenner MJ, Warren Z, Williams AR, Amoakohene E, Bakian AV, Bilder DA, Durkin MS, Fitzgerald RT, Furnier SM, Hughes MM, Ladd-Acosta CM, McArthur D, Pas ET, Salinas A, Vehorn A, Williams S, Esler A, Grzybowski A, Hall-Lande J, Nguyen RHN, Pierce K, Zahorodny W, Hudson A, Hallas L, Mancilla KC, Patrick M, Shenouda J, Sidwell K, DiRienzo M, Gutierrez J, Spivey MH, Lopez M, Pettygrove S, Schwenk YD, Washington A, Shaw KA
MMWR Surveill Summ 2023 Mar 24;72(2):1-14. doi: 10.15585/mmwr.ss7202a1. PMID: 36952288Free PMC Article
Gavril EC, Nucă I, Pânzaru MC, Ivanov AV, Mihai CT, Antoci LM, Ciobanu CG, Rusu C, Popescu R
Genes (Basel) 2023 Feb 11;14(2) doi: 10.3390/genes14020465. PMID: 36833393Free PMC Article
Velmans C, O'Donnell-Luria AH, Argilli E, Tran Mau-Them F, Vitobello A, Chan MC, Fung JL, Rech M, Abicht A, Aubert Mucca M, Carmichael J, Chassaing N, Clark R, Coubes C, Denommé-Pichon AS, de Dios JK, England E, Funalot B, Gerard M, Joseph M, Kennedy C, Kumps C, Willems M, van de Laar IMBH, Aarts-Tesselaar C, van Slegtenhorst M, Lehalle D, Leppig K, Lessmeier L, Pais LS, Paterson H, Ramanathan S, Rodan LH, Superti-Furga A, Chung BHY, Sherr E, Netzer C, Schaaf CP, Erger F
J Med Genet 2022 Jul;59(7):697-705. Epub 2021 Jul 28 doi: 10.1136/jmedgenet-2020-107470. PMID: 34321323Free PMC Article
Zablotsky B, Black LI, Maenner MJ, Schieve LA, Danielson ML, Bitsko RH, Blumberg SJ, Kogan MD, Boyle CA
Pediatrics 2019 Oct;144(4) doi: 10.1542/peds.2019-0811. PMID: 31558576Free PMC Article
Baio J, Wiggins L, Christensen DL, Maenner MJ, Daniels J, Warren Z, Kurzius-Spencer M, Zahorodny W, Robinson Rosenberg C, White T, Durkin MS, Imm P, Nikolaou L, Yeargin-Allsopp M, Lee LC, Harrington R, Lopez M, Fitzgerald RT, Hewitt A, Pettygrove S, Constantino JN, Vehorn A, Shenouda J, Hall-Lande J, Van Naarden Braun K, Dowling NF
MMWR Surveill Summ 2018 Apr 27;67(6):1-23. doi: 10.15585/mmwr.ss6706a1. PMID: 29701730Free PMC Article

Therapy

Frank Y
Pediatr Neurol 2021 Sep;122:59-64. Epub 2021 Jun 16 doi: 10.1016/j.pediatrneurol.2021.06.002. PMID: 34325981
Naczk A, Gajewska E, Naczk M
Int J Environ Res Public Health 2021 Jul 12;18(14) doi: 10.3390/ijerph18147441. PMID: 34299891Free PMC Article
Trivisano M, Specchio N
Epilepsy Behav 2019 Dec;101(Pt B):106539. Epub 2019 Oct 31 doi: 10.1016/j.yebeh.2019.106539. PMID: 31678000
Arends JBAM
Epilepsia 2018 Jun;59 Suppl 1:30-35. Epub 2018 Apr 9 doi: 10.1111/epi.14053. PMID: 29635767
Turner BJ, Austin SB, Chapman AL
Can J Psychiatry 2014 Nov;59(11):576-85. doi: 10.1177/070674371405901103. PMID: 25565473Free PMC Article

Prognosis

Stamberger H, Crosiers D, Balagura G, Bonardi CM, Basu A, Cantalupo G, Chiesa V, Christensen J, Dalla Bernardina B, Ellis CA, Furia F, Gardiner F, Giron C, Guerrini R, Klein KM, Korff C, Krijtova H, Leffler M, Lerche H, Lesca G, Lewis-Smith D, Marini C, Marjanovic D, Mazzola L, McKeown Ruggiero S, Mochel F, Ramond F, Reif PS, Richard-Mornas A, Rosenow F, Schropp C, Thomas RH, Vignoli A, Weber Y, Palmer E, Helbig I, Scheffer IE, Striano P, Møller RS, Gardella E, Weckhuysen S
Neurology 2022 Jul 19;99(3):e221-e233. Epub 2022 Jun 3 doi: 10.1212/WNL.0000000000200715. PMID: 35851549Free PMC Article
Juneja M, Gupta A, Sairam S, Jain R, Sharma M, Thadani A, Srinivasan R, Lingappa L, Ahmed S, Multani KS, Buch P, Chatterjee N, Dalwai S, Kabra M, Kapoor S, Patel PK, Girisha KM, Kulkarni M, Kunju PAM, Malhi P, Meenai Z, Mishra D, Mundkur N, Nair MKC, Oommen SP, Prasad C, Singh A, Srivastava L, Suman P, Thakur R
Indian Pediatr 2022 May 15;59(5):401-415. Epub 2022 Feb 19 PMID: 35188106
Groeneweg S, van Geest FS, Abacı A, Alcantud A, Ambegaonkar GP, Armour CM, Bakhtiani P, Barca D, Bertini ES, van Beynum IM, Brunetti-Pierri N, Bugiani M, Cappa M, Cappuccio G, Castellotti B, Castiglioni C, Chatterjee K, de Coo IFM, Coutant R, Craiu D, Crock P, DeGoede C, Demir K, Dica A, Dimitri P, Dolcetta-Capuzzo A, Dremmen MHG, Dubey R, Enderli A, Fairchild J, Gallichan J, George B, Gevers EF, Hackenberg A, Halász Z, Heinrich B, Huynh T, Kłosowska A, van der Knaap MS, van der Knoop MM, Konrad D, Koolen DA, Krude H, Lawson-Yuen A, Lebl J, Linder-Lucht M, Lorea CF, Lourenço CM, Lunsing RJ, Lyons G, Malikova J, Mancilla EE, McGowan A, Mericq V, Lora FM, Moran C, Müller KE, Oliver-Petit I, Paone L, Paul PG, Polak M, Porta F, Poswar FO, Reinauer C, Rozenkova K, Menevse TS, Simm P, Simon A, Singh Y, Spada M, van der Spek J, Stals MAM, Stoupa A, Subramanian GM, Tonduti D, Turan S, den Uil CA, Vanderniet J, van der Walt A, Wémeau JL, Wierzba J, de Wit MY, Wolf NI, Wurm M, Zibordi F, Zung A, Zwaveling-Soonawala N, Visser WE
Lancet Diabetes Endocrinol 2020 Jul;8(7):594-605. doi: 10.1016/S2213-8587(20)30153-4. PMID: 32559475Free PMC Article
Dalsgaard S, Thorsteinsson E, Trabjerg BB, Schullehner J, Plana-Ripoll O, Brikell I, Wimberley T, Thygesen M, Madsen KB, Timmerman A, Schendel D, McGrath JJ, Mortensen PB, Pedersen CB
JAMA Psychiatry 2020 Feb 1;77(2):155-164. doi: 10.1001/jamapsychiatry.2019.3523. PMID: 31746968Free PMC Article
Arends JBAM
Epilepsia 2018 Jun;59 Suppl 1:30-35. Epub 2018 Apr 9 doi: 10.1111/epi.14053. PMID: 29635767

Clinical prediction guides

Maenner MJ, Warren Z, Williams AR, Amoakohene E, Bakian AV, Bilder DA, Durkin MS, Fitzgerald RT, Furnier SM, Hughes MM, Ladd-Acosta CM, McArthur D, Pas ET, Salinas A, Vehorn A, Williams S, Esler A, Grzybowski A, Hall-Lande J, Nguyen RHN, Pierce K, Zahorodny W, Hudson A, Hallas L, Mancilla KC, Patrick M, Shenouda J, Sidwell K, DiRienzo M, Gutierrez J, Spivey MH, Lopez M, Pettygrove S, Schwenk YD, Washington A, Shaw KA
MMWR Surveill Summ 2023 Mar 24;72(2):1-14. doi: 10.15585/mmwr.ss7202a1. PMID: 36952288Free PMC Article
Gavril EC, Nucă I, Pânzaru MC, Ivanov AV, Mihai CT, Antoci LM, Ciobanu CG, Rusu C, Popescu R
Genes (Basel) 2023 Feb 11;14(2) doi: 10.3390/genes14020465. PMID: 36833393Free PMC Article
Wiśniewska K, Wolski J, Gaffke L, Cyske Z, Pierzynowska K, Węgrzyn G
J Appl Genet 2022 Sep;63(3):475-495. Epub 2022 May 13 doi: 10.1007/s13353-022-00703-1. PMID: 35562626
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
Baio J, Wiggins L, Christensen DL, Maenner MJ, Daniels J, Warren Z, Kurzius-Spencer M, Zahorodny W, Robinson Rosenberg C, White T, Durkin MS, Imm P, Nikolaou L, Yeargin-Allsopp M, Lee LC, Harrington R, Lopez M, Fitzgerald RT, Hewitt A, Pettygrove S, Constantino JN, Vehorn A, Shenouda J, Hall-Lande J, Van Naarden Braun K, Dowling NF
MMWR Surveill Summ 2018 Apr 27;67(6):1-23. doi: 10.15585/mmwr.ss6706a1. PMID: 29701730Free PMC Article

Recent systematic reviews

Barišić A, Ravančić ME, Majstorivić D, Vraneković J
J Intellect Disabil Res 2023 Aug;67(8):701-719. Epub 2023 May 22 doi: 10.1111/jir.13042. PMID: 37218392
Vi L, Jiwa MI, Lunsky Y, Thakur A
BMC Med Educ 2023 May 11;23(1):329. doi: 10.1186/s12909-023-04259-4. PMID: 37170246Free PMC Article
GBD 2019 Mental Disorders Collaborators
Lancet Psychiatry 2022 Feb;9(2):137-150. Epub 2022 Jan 10 doi: 10.1016/S2215-0366(21)00395-3. PMID: 35026139Free 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
Turner BJ, Austin SB, Chapman AL
Can J Psychiatry 2014 Nov;59(11):576-85. doi: 10.1177/070674371405901103. PMID: 25565473Free PMC Article

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