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Neurodevelopmental disorder with language delay and variable cognitive abnormalities(NEDLC)

MedGen UID:
1850358
Concept ID:
C5882689
Disease or Syndrome
Synonym: NEDLC
 
Gene (location): GABBR1 (6p22.1)
 
Monarch Initiative: MONDO:0957779
OMIM®: 620502

Definition

Neurodevelopmental disorder with language delay and variable cognitive abnormalities (NEDLC) is a phenotypically heterogeneous neurologic disorder. Affected individuals may show early motor delay, speech and language delay, impaired intellectual development, learning disabilities, and/or behavioral abnormalities, although the severity and manifestations vary widely. Repetitive behavior and sleep difficulties are commonly present. More severe features include seizures, hypotonia, ocular abnormalities, dysmorphic features, and psychiatric comorbidities (Cediel et al., 2022). [from OMIM]

Clinical features

From HPO
Encopresis
MedGen UID:
754509
Concept ID:
C2945606
Sign or Symptom
Clinodactyly of the 5th finger
MedGen UID:
340456
Concept ID:
C1850049
Congenital Abnormality
Clinodactyly refers to a bending or curvature of the fifth finger in the radial direction (i.e., towards the 4th finger).
Increased femoral anteversion
MedGen UID:
868511
Concept ID:
C4022909
Finding
An increased degree of femoral version, which is defined as the angular difference between axis of femoral neck and transcondylar axis of the knee. Thus, femoral anteversion is an inward twisting of the femur that causes the knees and feet to turn inward.
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.
Motor stereotypies
MedGen UID:
21318
Concept ID:
C0038271
Individual Behavior
Use of the same abnormal action in response to certain triggers or at random. They may be used as a way to regulate one's internal state but must otherwise have no apparent functional purpose.
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.
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.
Attention deficit hyperactivity disorder
MedGen UID:
220387
Concept ID:
C1263846
Mental or Behavioral Dysfunction
Attention-deficit/hyperactivity disorder (ADHD) is a behavioral disorder that typically begins in childhood and is characterized by a short attention span (inattention), an inability to be calm and stay still (hyperactivity), and poor impulse control (impulsivity). Some people with ADHD have problems with only inattention or with hyperactivity and impulsivity, but most have problems related to all three features.\n\nIn people with ADHD, the characteristic behaviors are frequent and severe enough to interfere with the activities of daily living such as school, work, and relationships with others. Because of an inability to stay focused on tasks, people with inattention may be easily distracted, forgetful, avoid tasks that require sustained attention, have difficulty organizing tasks, or frequently lose items.\n\nHyperactivity is usually shown by frequent movement. Individuals with this feature often fidget or tap their foot when seated, leave their seat when it is inappropriate to do so (such as in the classroom), or talk a lot and interrupt others.\n\nIn most affected individuals, ADHD continues throughout life, but in about one-third of individuals, signs and symptoms of ADHD go away by adulthood.\n\nImpulsivity can result in hasty actions without thought for the consequences. Individuals with poor impulse control may have difficulty waiting for their turn, deferring to others, or considering their actions before acting.\n\nMore than two-thirds of all individuals with ADHD have additional conditions, including insomnia, mood or anxiety disorders, learning disorders, or substance use disorders. Affected individuals may also have autism spectrum disorder, which is characterized by impaired communication and social interaction, or Tourette syndrome, which is a disorder characterized by repetitive and involuntary movements or noises called tics.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
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.
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.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
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.
Dry skin
MedGen UID:
56250
Concept ID:
C0151908
Sign or Symptom
Skin characterized by the lack of natural or normal moisture.
Nail dystrophy
MedGen UID:
66368
Concept ID:
C0221260
Disease or Syndrome
Onychodystrophy (nail dystrophy) refers to nail changes apart from changes of the color (nail dyschromia) and involves partial or complete disruption of the various keratinous layers of the nail plate.
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.
Optic nerve hypoplasia
MedGen UID:
137901
Concept ID:
C0338502
Disease or Syndrome
Underdevelopment of the optic nerve.

Professional guidelines

PubMed

Miroševič Š, Khandelwal S, Sušjan P, Žakelj N, Gosar D, Forstnerič V, Lainšček D, Jerala R, Osredkar D
Int J Mol Sci 2022 Oct 19;23(20) doi: 10.3390/ijms232012564. PMID: 36293418Free PMC Article
Ousley O, Rockers K, Dell ML, Coleman K, Cubells JF
Curr Psychiatry Rep 2007 Apr;9(2):148-58. doi: 10.1007/s11920-007-0085-8. PMID: 17389127

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
Miroševič Š, Khandelwal S, Sušjan P, Žakelj N, Gosar D, Forstnerič V, Lainšček D, Jerala R, Osredkar D
Int J Mol Sci 2022 Oct 19;23(20) doi: 10.3390/ijms232012564. PMID: 36293418Free PMC Article
Galli J, Loi E, Morandi A, Scaglioni V, Rossi A, Molinaro A, Pasini N, Semeraro F, Ruberto G, Fazzi E
Neuropediatrics 2022 Feb;53(1):7-14. Epub 2021 Jul 29 doi: 10.1055/s-0041-1732430. PMID: 34327695
Van Den Heuvel E, Manders E, Swillen A, Zink I
J Commun Disord 2018 Sep-Oct;75:37-56. Epub 2018 Jun 5 doi: 10.1016/j.jcomdis.2018.06.001. PMID: 30005318
Swillen A, McDonald-McGinn D
Am J Med Genet C Semin Med Genet 2015 Jun;169(2):172-81. Epub 2015 May 18 doi: 10.1002/ajmg.c.31435. PMID: 25989227Free PMC Article

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
Ward R, Sanoudaki E
Clin Linguist Phon 2021 Jul 3;35(7):663-689. Epub 2020 Oct 12 doi: 10.1080/02699206.2020.1818288. PMID: 33045862
Guo H, Li Y, Shen L, Wang T, Jia X, Liu L, Xu T, Ou M, Hoekzema K, Wu H, Gillentine MA, Liu C, Ni H, Peng P, Zhao R, Zhang Y, Phornphutkul C, Stegmann APA, Prada CE, Hopkin RJ, Shieh JT, McWalter K, Monaghan KG, van Hasselt PM, van Gassen K, Bai T, Long M, Han L, Quan Y, Chen M, Zhang Y, Li K, Zhang Q, Tan J, Zhu T, Liu Y, Pang N, Peng J, Scott DA, Lalani SR, Azamian M, Mancini GMS, Adams DJ, Kvarnung M, Lindstrand A, Nordgren A, Pevsner J, Osei-Owusu IA, Romano C, Calabrese G, Galesi O, Gecz J, Haan E, Ranells J, Racobaldo M, Nordenskjold M, Madan-Khetarpal S, Sebastian J, Ball S, Zou X, Zhao J, Hu Z, Xia F, Liu P, Rosenfeld JA, de Vries BBA, Bernier RA, Xu ZD, Li H, Xie W, Hufnagel RB, Eichler EE, Xia K
Sci Adv 2019 Sep;5(9):eaax2166. Epub 2019 Sep 25 doi: 10.1126/sciadv.aax2166. PMID: 31579823Free PMC Article
Gallagher ER, Collett BR
Pediatrics 2019 Jul;144(1) Epub 2019 Jun 12 doi: 10.1542/peds.2018-4027. PMID: 31189616
Antshel KM, Kates WR, Roizen N, Fremont W, Shprintzen RJ
Child Neuropsychol 2005 Feb;11(1):5-19. doi: 10.1080/09297040590911185. PMID: 15823980

Therapy

Smith R, Ntsiea V, Brown S, Potterton J
Cardiovasc J Afr 2022 May-Jun 23;33(3):145-152. Epub 2022 Jan 13 doi: 10.5830/CVJA-2021-057. PMID: 35076652Free PMC Article
Samango-Sprouse CA, Tran SL, Lasutschinkow PC, Sadeghin T, Powell S, Mitchell FL, Gropman A
Am J Med Genet A 2020 Aug;182(8):1881-1889. Epub 2020 Mar 27 doi: 10.1002/ajmg.a.61561. PMID: 32220052
Joseph L, Farmer C, Chlebowski C, Henry L, Fish A, Mankiw C, Xenophontos A, Clasen L, Sauls B, Seidlitz J, Blumenthal J, Torres E, Thurm A, Raznahan A
J Neurodev Disord 2018 Oct 22;10(1):30. doi: 10.1186/s11689-018-9248-7. PMID: 30348076Free PMC Article
Soto CB, Olude O, Hoffmann RG, Bear L, Chin A, Dasgupta M, Mussatto K
Congenit Heart Dis 2011 Sep-Oct;6(5):451-60. Epub 2011 Jul 1 doi: 10.1111/j.1747-0803.2011.00546.x. PMID: 21718458
Elsabbagh M, Cohen H, Cohen M, Rosen S, Karmiloff-Smith A
J Intellect Disabil Res 2011 Jun;55(6):563-71. Epub 2011 Mar 15 doi: 10.1111/j.1365-2788.2011.01411.x. PMID: 21557785

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
Bhattacharjee I, Mohamed MA, Nandakumar V, Friedman NR, Ruggieri P, Aly H
Early Hum Dev 2022 Jun;169:105574. Epub 2022 Apr 25 doi: 10.1016/j.earlhumdev.2022.105574. PMID: 35561519
Jilek E, Shields A, Zhang L, Simpson P, Bear L, Martins SA, Mussatto KA, Brosig CL
Cardiol Young 2022 Aug;32(8):1216-1221. Epub 2021 Sep 22 doi: 10.1017/S1047951121003942. PMID: 34548125
den Hoed J, de Boer E, Voisin N, Dingemans AJM, Guex N, Wiel L, Nellaker C, Amudhavalli SM, Banka S, Bena FS, Ben-Zeev B, Bonagura VR, Bruel AL, Brunet T, Brunner HG, Chew HB, Chrast J, Cimbalistienė L, Coon H; DDD Study, Délot EC, Démurger F, Denommé-Pichon AS, Depienne C, Donnai D, Dyment DA, Elpeleg O, Faivre L, Gilissen C, Granger L, Haber B, Hachiya Y, Abedi YH, Hanebeck J, Hehir-Kwa JY, Horist B, Itai T, Jackson A, Jewell R, Jones KL, Joss S, Kashii H, Kato M, Kattentidt-Mouravieva AA, Kok F, Kotzaeridou U, Krishnamurthy V, Kučinskas V, Kuechler A, Lavillaureix A, Liu P, Manwaring L, Matsumoto N, Mazel B, McWalter K, Meiner V, Mikati MA, Miyatake S, Mizuguchi T, Moey LH, Mohammed S, Mor-Shaked H, Mountford H, Newbury-Ecob R, Odent S, Orec L, Osmond M, Palculict TB, Parker M, Petersen AK, Pfundt R, Preikšaitienė E, Radtke K, Ranza E, Rosenfeld JA, Santiago-Sim T, Schwager C, Sinnema M, Snijders Blok L, Spillmann RC, Stegmann APA, Thiffault I, Tran L, Vaknin-Dembinsky A, Vedovato-Dos-Santos JH, Schrier Vergano SA, Vilain E, Vitobello A, Wagner M, Waheeb A, Willing M, Zuccarelli B, Kini U, Newbury DF, Kleefstra T, Reymond A, Fisher SE, Vissers LELM
Am J Hum Genet 2021 Feb 4;108(2):346-356. Epub 2021 Jan 28 doi: 10.1016/j.ajhg.2021.01.007. PMID: 33513338Free PMC Article
Swillen A, McDonald-McGinn D
Am J Med Genet C Semin Med Genet 2015 Jun;169(2):172-81. Epub 2015 May 18 doi: 10.1002/ajmg.c.31435. PMID: 25989227Free 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
Miroševič Š, Khandelwal S, Sušjan P, Žakelj N, Gosar D, Forstnerič V, Lainšček D, Jerala R, Osredkar D
Int J Mol Sci 2022 Oct 19;23(20) doi: 10.3390/ijms232012564. PMID: 36293418Free PMC Article
den Hoed J, de Boer E, Voisin N, Dingemans AJM, Guex N, Wiel L, Nellaker C, Amudhavalli SM, Banka S, Bena FS, Ben-Zeev B, Bonagura VR, Bruel AL, Brunet T, Brunner HG, Chew HB, Chrast J, Cimbalistienė L, Coon H; DDD Study, Délot EC, Démurger F, Denommé-Pichon AS, Depienne C, Donnai D, Dyment DA, Elpeleg O, Faivre L, Gilissen C, Granger L, Haber B, Hachiya Y, Abedi YH, Hanebeck J, Hehir-Kwa JY, Horist B, Itai T, Jackson A, Jewell R, Jones KL, Joss S, Kashii H, Kato M, Kattentidt-Mouravieva AA, Kok F, Kotzaeridou U, Krishnamurthy V, Kučinskas V, Kuechler A, Lavillaureix A, Liu P, Manwaring L, Matsumoto N, Mazel B, McWalter K, Meiner V, Mikati MA, Miyatake S, Mizuguchi T, Moey LH, Mohammed S, Mor-Shaked H, Mountford H, Newbury-Ecob R, Odent S, Orec L, Osmond M, Palculict TB, Parker M, Petersen AK, Pfundt R, Preikšaitienė E, Radtke K, Ranza E, Rosenfeld JA, Santiago-Sim T, Schwager C, Sinnema M, Snijders Blok L, Spillmann RC, Stegmann APA, Thiffault I, Tran L, Vaknin-Dembinsky A, Vedovato-Dos-Santos JH, Schrier Vergano SA, Vilain E, Vitobello A, Wagner M, Waheeb A, Willing M, Zuccarelli B, Kini U, Newbury DF, Kleefstra T, Reymond A, Fisher SE, Vissers LELM
Am J Hum Genet 2021 Feb 4;108(2):346-356. Epub 2021 Jan 28 doi: 10.1016/j.ajhg.2021.01.007. PMID: 33513338Free PMC Article
Van Den Heuvel E, Manders E, Swillen A, Zink I
J Commun Disord 2018 Sep-Oct;75:37-56. Epub 2018 Jun 5 doi: 10.1016/j.jcomdis.2018.06.001. PMID: 30005318
Swillen A, McDonald-McGinn D
Am J Med Genet C Semin Med Genet 2015 Jun;169(2):172-81. Epub 2015 May 18 doi: 10.1002/ajmg.c.31435. PMID: 25989227Free 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
Miroševič Š, Khandelwal S, Sušjan P, Žakelj N, Gosar D, Forstnerič V, Lainšček D, Jerala R, Osredkar D
Int J Mol Sci 2022 Oct 19;23(20) doi: 10.3390/ijms232012564. PMID: 36293418Free PMC Article
Gallagher ER, Collett BR
Pediatrics 2019 Jul;144(1) Epub 2019 Jun 12 doi: 10.1542/peds.2018-4027. PMID: 31189616
Siffredi V, Anderson V, Leventer RJ, Spencer-Smith MM
Dev Neuropsychol 2013;38(1):36-57. doi: 10.1080/87565641.2012.721421. PMID: 23311314

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