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Intellectual developmental disorder with short stature and behavioral abnormalities(IDDSSBA)

MedGen UID:
1684812
Concept ID:
C5231462
Disease or Syndrome
Synonyms: IDDSSBA; INTELLECTUAL DEVELOPMENTAL DISORDER WITH SHORT STATURE AND BEHAVIORAL ABNORMALITIES
 
Gene (location): IQSEC1 (3p25.2-25.1)
 
Monarch Initiative: MONDO:0032870
OMIM®: 618687

Clinical features

From HPO
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).
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.
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.
Status epilepticus
MedGen UID:
11586
Concept ID:
C0038220
Disease or Syndrome
Status epilepticus is a type of prolonged seizure resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms which lead to abnormally prolonged seizures (after time point t1). It is a condition that can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures.
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.
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).
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.
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.
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\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\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\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.
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Visual impairment
MedGen UID:
777085
Concept ID:
C3665347
Finding
Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.

Professional guidelines

PubMed

Braga BL, da Cunha Scalco R, Homma TK, Freire BL, Cellin LP, Canton APM, Lerario AM, de Assis Funari MF, de Souza V, Bertola DR, Malaquias AC, Mendonca BB, de Lima Jorge AA
Clin Genet 2025 Apr;107(4):441-445. Epub 2024 Nov 25 doi: 10.1111/cge.14659. PMID: 39586716
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
Butler MG, Miller JL, Forster JL
Curr Pediatr Rev 2019;15(4):207-244. doi: 10.2174/1573396315666190716120925. PMID: 31333129Free PMC Article

Recent clinical studies

Etiology

Höybye C, Tauber M
J Clin Endocrinol Metab 2022 May 17;107(6):1698-1705. doi: 10.1210/clinem/dgac082. PMID: 35150573Free PMC Article
Van Dijck A, Vulto-van Silfhout AT, Cappuyns E, van der Werf IM, Mancini GM, Tzschach A, Bernier R, Gozes I, Eichler EE, Romano C, Lindstrand A, Nordgren A; ADNP Consortium, Kvarnung M, Kleefstra T, de Vries BBA, Küry S, Rosenfeld JA, Meuwissen ME, Vandeweyer G, Kooy RF
Biol Psychiatry 2019 Feb 15;85(4):287-297. Epub 2018 Mar 15 doi: 10.1016/j.biopsych.2018.02.1173. PMID: 29724491Free PMC Article
Priolo M, Schanze D, Tatton-Brown K, Mulder PA, Tenorio J, Kooblall K, Acero IH, Alkuraya FS, Arias P, Bernardini L, Bijlsma EK, Cole T, Coubes C, Dapia I, Davies S, Di Donato N, Elcioglu NH, Fahrner JA, Foster A, González NG, Huber I, Iascone M, Kaiser AS, Kamath A, Liebelt J, Lynch SA, Maas SM, Mammì C, Mathijssen IB, McKee S, Menke LA, Mirzaa GM, Montgomery T, Neubauer D, Neumann TE, Pintomalli L, Pisanti MA, Plomp AS, Price S, Salter C, Santos-Simarro F, Sarda P, Segovia M, Shaw-Smith C, Smithson S, Suri M, Valdez RM, Van Haeringen A, Van Hagen JM, Zollino M, Lapunzina P, Thakker RV, Zenker M, Hennekam RC
Hum Mutat 2018 Sep;39(9):1226-1237. Epub 2018 Jun 25 doi: 10.1002/humu.23563. PMID: 29897170Free PMC Article
Le Goff C, Michot C, Cormier-Daire V
Clin Genet 2014 Jun;85(6):503-13. Epub 2014 Apr 2 doi: 10.1111/cge.12365. PMID: 24580733
Cassidy SB, Schwartz S, Miller JL, Driscoll DJ
Genet Med 2012 Jan;14(1):10-26. Epub 2011 Sep 26 doi: 10.1038/gim.0b013e31822bead0. PMID: 22237428

Diagnosis

Danowitz M, Grimberg A
Adv Pediatr 2022 Aug;69(1):203-217. Epub 2022 Jun 17 doi: 10.1016/j.yapd.2022.03.005. PMID: 35985710Free PMC Article
Butler MG, Miller JL, Forster JL
Curr Pediatr Rev 2019;15(4):207-244. doi: 10.2174/1573396315666190716120925. PMID: 31333129Free PMC Article
Priolo M, Schanze D, Tatton-Brown K, Mulder PA, Tenorio J, Kooblall K, Acero IH, Alkuraya FS, Arias P, Bernardini L, Bijlsma EK, Cole T, Coubes C, Dapia I, Davies S, Di Donato N, Elcioglu NH, Fahrner JA, Foster A, González NG, Huber I, Iascone M, Kaiser AS, Kamath A, Liebelt J, Lynch SA, Maas SM, Mammì C, Mathijssen IB, McKee S, Menke LA, Mirzaa GM, Montgomery T, Neubauer D, Neumann TE, Pintomalli L, Pisanti MA, Plomp AS, Price S, Salter C, Santos-Simarro F, Sarda P, Segovia M, Shaw-Smith C, Smithson S, Suri M, Valdez RM, Van Haeringen A, Van Hagen JM, Zollino M, Lapunzina P, Thakker RV, Zenker M, Hennekam RC
Hum Mutat 2018 Sep;39(9):1226-1237. Epub 2018 Jun 25 doi: 10.1002/humu.23563. PMID: 29897170Free PMC Article
Angulo MA, Butler MG, Cataletto ME
J Endocrinol Invest 2015 Dec;38(12):1249-63. Epub 2015 Jun 11 doi: 10.1007/s40618-015-0312-9. PMID: 26062517Free PMC Article
Cassidy SB, Schwartz S, Miller JL, Driscoll DJ
Genet Med 2012 Jan;14(1):10-26. Epub 2011 Sep 26 doi: 10.1038/gim.0b013e31822bead0. PMID: 22237428

Therapy

Kucharska A, Witkowska-Sędek E, Erazmus M, Artemniak-Wojtowicz D, Krajewska M, Pyrżak B
Int J Mol Sci 2024 Sep 22;25(18) doi: 10.3390/ijms251810169. PMID: 39337654Free PMC Article
Schmok T, Surampalli A, Khare M, Zandihaghighi S, Baghbaninogourani R, Patolia B, Gold JA, Naidu A, Cassidy SB, Kimonis VE
Am J Med Genet A 2024 Oct;194(10):e63724. Epub 2024 Jun 4 doi: 10.1002/ajmg.a.63724. PMID: 38837660
Bergamasco MI, Vanyai HK, Garnham AL, Geoghegan ND, Vogel AP, Eccles S, Rogers KL, Smyth GK, Blewitt ME, Hannan AJ, Thomas T, Voss AK
J Clin Invest 2024 Apr 1;134(7) doi: 10.1172/JCI167672. PMID: 38557491Free PMC Article
Danowitz M, Grimberg A
Adv Pediatr 2022 Aug;69(1):203-217. Epub 2022 Jun 17 doi: 10.1016/j.yapd.2022.03.005. PMID: 35985710Free PMC Article
Cassidy SB, Driscoll DJ
Eur J Hum Genet 2009 Jan;17(1):3-13. Epub 2008 Sep 10 doi: 10.1038/ejhg.2008.165. PMID: 18781185Free PMC Article

Prognosis

Bruselles A, Mancini C, Chiriatti L, Carvetta M, Baroni MC, Cappelletti C, Caraffi SG, Celario M, Ciolfi A, Cordeddu V, De Falco A, Ferilli M, Garavelli L, Leoni C, Meossi C, Niceta M, Onesimo R, Peluso F, Politano D, Priolo M, Radio FC, Santorelli F, Signorini S, Sirchia F, Valente EM, Zampino G, Tartaglia M
Eur J Hum Genet 2025 Apr;33(4):432-440. Epub 2025 Feb 26 doi: 10.1038/s41431-025-01820-1. PMID: 40011755Free PMC Article
Pan X, Liu L, Zhang X, Tang X, Qian G, Qiu H, Lin S, Yao H, Dong X, Tan B
J Hum Genet 2024 Aug;69(8):391-400. Epub 2024 May 13 doi: 10.1038/s10038-024-01255-4. PMID: 38740982
Höybye C, Tauber M
J Clin Endocrinol Metab 2022 May 17;107(6):1698-1705. doi: 10.1210/clinem/dgac082. PMID: 35150573Free PMC Article
Butler MG, Manzardo AM, Forster JL
Curr Pediatr Rev 2016;12(2):136-66. doi: 10.2174/1573396312666151123115250. PMID: 26592417Free PMC Article
Le Goff C, Michot C, Cormier-Daire V
Clin Genet 2014 Jun;85(6):503-13. Epub 2014 Apr 2 doi: 10.1111/cge.12365. PMID: 24580733

Clinical prediction guides

Urakawa T, Soejima H, Yamoto K, Hara-Isono K, Nakamura A, Kawashima S, Narusawa H, Kosaki R, Nishimura Y, Yamazawa K, Hattori T, Muramatsu Y, Inoue T, Matsubara K, Fukami M, Saitoh S, Ogata T, Kagami M
Clin Epigenetics 2024 Oct 5;16(1):138. doi: 10.1186/s13148-024-01744-5. PMID: 39369220Free PMC Article
Huang Y, Jay KL, Yen-Wen Huang A, Wan J, Jangam SV, Chorin O, Rothschild A, Barel O, Mariani M, Iascone M, Xue H; Undiagnosed Diseases Network, Huang J, Mignot C, Keren B, Saillour V, Mah-Som AY, Sacharow S, Rajabi F, Costin C, Yamamoto S, Kanca O, Bellen HJ, Rosenfeld JA, Palmer CGS, Nelson SF, Wangler MF, Martinez-Agosto JA
Genet Med 2024 Nov;26(11):101218. Epub 2024 Jul 19 doi: 10.1016/j.gim.2024.101218. PMID: 39036895Free PMC Article
Pan X, Liu L, Zhang X, Tang X, Qian G, Qiu H, Lin S, Yao H, Dong X, Tan B
J Hum Genet 2024 Aug;69(8):391-400. Epub 2024 May 13 doi: 10.1038/s10038-024-01255-4. PMID: 38740982
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
de Sousa Lima Strafacci A, Fernandes Camargo J, Bertapelli F, Guerra Júnior G
J Appl Genet 2020 May;61(2):205-212. Epub 2020 Mar 10 doi: 10.1007/s13353-020-00551-x. PMID: 32157657

Recent systematic reviews

Kucharska A, Witkowska-Sędek E, Erazmus M, Artemniak-Wojtowicz D, Krajewska M, Pyrżak B
Int J Mol Sci 2024 Sep 22;25(18) doi: 10.3390/ijms251810169. PMID: 39337654Free PMC Article
Orso M, Polistena B, Granato S, Novelli G, Di Virgilio R, La Torre D, d'Angela D, Spandonaro F
PLoS One 2022;17(2):e0264403. Epub 2022 Feb 25 doi: 10.1371/journal.pone.0264403. PMID: 35213607Free PMC Article
de Sousa Lima Strafacci A, Fernandes Camargo J, Bertapelli F, Guerra Júnior G
J Appl Genet 2020 May;61(2):205-212. Epub 2020 Mar 10 doi: 10.1007/s13353-020-00551-x. PMID: 32157657

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