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Intellectual developmental disorder with short stature and variable skeletal anomalies(IDDSSA)

MedGen UID:
1680968
Concept ID:
C5193105
Disease or Syndrome
Synonyms: IDDSSA; INTELLECTUAL DEVELOPMENTAL DISORDER WITH SHORT STATURE AND VARIABLE SKELETAL ANOMALIES
 
Gene (location): WIPI2 (7p22.1)
 
Monarch Initiative: MONDO:0032759
OMIM®: 618453

Clinical features

From HPO
Short thumb
MedGen UID:
98469
Concept ID:
C0431890
Congenital Abnormality
Hypoplasia (congenital reduction in size) of the thumb.
Overlapping toe
MedGen UID:
182531
Concept ID:
C0920299
Anatomical Abnormality
Describes a foot digit resting on the dorsal surface of an adjacent digit when the foot is at rest. Initially clawing may be dynamic and only noticeable on walking. Over time the plantar plate tears, subluxation occurs at the metatarsophalangeal joint (MTPJ), and the deformity becomes permanent.
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).
Cardiac arrhythmia
MedGen UID:
2039
Concept ID:
C0003811
Finding
Any cardiac rhythm other than the normal sinus rhythm. Such a rhythm may be either of sinus or ectopic origin and either regular or irregular. An arrhythmia may be due to a disturbance in impulse formation or conduction or both.
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).
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Dyskinesia
MedGen UID:
8514
Concept ID:
C0013384
Disease or Syndrome
A movement disorder which consists of effects including diminished voluntary movements and the presence of involuntary movements.
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.
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
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
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Exaggerated anterior convexity of the thoracic vertebral column.
Camptodactyly
MedGen UID:
195780
Concept ID:
C0685409
Congenital Abnormality
The distal interphalangeal joint and/or the proximal interphalangeal joint of the fingers or toes cannot be extended to 180 degrees by either active or passive extension.

Professional guidelines

PubMed

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
Girirajan S, Vlangos CN, Szomju BB, Edelman E, Trevors CD, Dupuis L, Nezarati M, Bunyan DJ, Elsea SH
Genet Med 2006 Jul;8(7):417-27. doi: 10.1097/01.gim.0000228215.32110.89. PMID: 16845274

Recent clinical studies

Etiology

Vasconcelos G, Stenehjem JS, Axelsson S, Saeves R
Orphanet J Rare Dis 2022 Feb 22;17(1):77. doi: 10.1186/s13023-022-02222-y. PMID: 35193626Free PMC Article
Wilson MP, Garanto A, Pinto E Vairo F, Ng BG, Ranatunga WK, Ventouratou M, Baerenfaenger M, Huijben K, Thiel C, Ashikov A, Keldermans L, Souche E, Vuillaumier-Barrot S, Dupré T, Michelakakis H, Fiumara A, Pitt J, White SM, Lim SC, Gallacher L, Peters H, Rymen D, Witters P, Ribes A, Morales-Romero B, Rodríguez-Palmero A, Ballhausen D, de Lonlay P, Barone R, Janssen MCH, Jaeken J, Freeze HH, Matthijs G, Morava E, Lefeber DJ
Am J Hum Genet 2021 Nov 4;108(11):2130-2144. Epub 2021 Oct 14 doi: 10.1016/j.ajhg.2021.09.012. PMID: 34653363Free PMC Article
Yabumoto M, Kianmahd J, Singh M, Palafox MF, Wei A, Elliott K, Goodloe DH, Dean SJ, Gooch C, Murray BK, Swartz E, Schrier Vergano SA, Towne MC, Nugent K, Roeder ER, Kresge C, Pletcher BA, Grand K, Graham JM Jr, Gates R, Gomez-Ospina N, Ramanathan S, Clark RD, Glaser K, Benke PJ, Cohen JS, Fatemi A, Mu W, Baranano KW, Madden JA, Gubbels CS, Yu TW, Agrawal PB, Chambers MK, Phornphutkul C, Pugh JA, Tauber KA, Azova S, Smith JR, O'Donnell-Luria A, Medsker H, Srivastava S, Krakow D, Schweitzer DN, Arboleda VA
Mol Genet Genomic Med 2021 Oct;9(10):e1809. Epub 2021 Sep 14 doi: 10.1002/mgg3.1809. PMID: 34519438Free PMC Article
Garavelli L, Maini I, Baccilieri F, Ivanovski I, Pollazzon M, Rosato S, Iughetti L, Unger S, Superti-Furga A, Tartaglia M
Eur J Pediatr 2016 Oct;175(10):1307-15. Epub 2016 Aug 25 doi: 10.1007/s00431-016-2761-3. PMID: 27562837
Axelrad ME, Glidden R, Nicholson L, Gripp KW
Am J Med Genet A 2004 Aug 1;128A(4):396-400. doi: 10.1002/ajmg.a.30140. PMID: 15264285

Diagnosis

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
Fennell AP, Baxter AE, Berkovic SF, Ellaway CJ, Forwood C, Hildebrand MS, Kumble S, McKeown C, Mowat D, Poke G, Rajagopalan S, Regan BM, Scheffer IE, Stark Z, Stutterd CA, Tan TY, Wilkins EJ, Yeung A, Hunter MF
Am J Med Genet A 2022 Dec;188(12):3432-3447. Epub 2022 Aug 17 doi: 10.1002/ajmg.a.62950. PMID: 36367278
Stoll C, Alembik Y, Dott B, Roth MP
Eur J Med Genet 2022 Nov;65(11):104612. Epub 2022 Sep 20 doi: 10.1016/j.ejmg.2022.104612. PMID: 36150686
Loberti L, Bruno LP, Granata S, Doddato G, Resciniti S, Fava F, Carullo M, Rahikkala E, Jouret G, Menke LA, Lederer D, Vrielynck P, Ryba L, Brunetti-Pierri N, Lasa-Aranzasti A, Cueto-González AM, Trujillano L, Valenzuela I, Tizzano EF, Spinelli AM, Bruno I, Currò A, Stanzial F, Benedicenti F, Lopergolo D, Santorelli FM, Aristidou C, Tanteles GA, Maystadt I, Tkemaladze T, Reimand T, Lokke H, Õunap K, Haanpää MK, Holubová A, Zoubková V, Schwarz M, Žordania R, Muru K, Roht L, Tihveräinen A, Teek R, Thomson U, Atallah I, Superti-Furga A, Buoni S, Canitano R, Scandurra V, Rossetti A, Grosso S, Battini R, Baldassarri M, Mencarelli MA, Rizzo CL, Bruttini M, Mari F, Ariani F, Renieri A, Pinto AM
Hum Mol Genet 2022 Dec 16;31(24):4131-4142. doi: 10.1093/hmg/ddac167. PMID: 35861666Free PMC Article
Vasconcelos G, Stenehjem JS, Axelsson S, Saeves R
Orphanet J Rare Dis 2022 Feb 22;17(1):77. doi: 10.1186/s13023-022-02222-y. PMID: 35193626Free PMC Article

Prognosis

Motta M, Fasano G, Gredy S, Brinkmann J, Bonnard AA, Simsek-Kiper PO, Gulec EY, Essaddam L, Utine GE, Guarnetti Prandi I, Venditti M, Pantaleoni F, Radio FC, Ciolfi A, Petrini S, Consoli F, Vignal C, Hepbasli D, Ullrich M, de Boer E, Vissers LELM, Gritli S, Rossi C, De Luca A, Ben Becher S, Gelb BD, Dallapiccola B, Lauri A, Chillemi G, Schuh K, Cavé H, Zenker M, Tartaglia M
Am J Hum Genet 2021 Nov 4;108(11):2112-2129. Epub 2021 Oct 8 doi: 10.1016/j.ajhg.2021.09.007. PMID: 34626534Free PMC Article
Douglas G, Cho MT, Telegrafi A, Winter S, Carmichael J, Zackai EH, Deardorff MA, Harr M, Williams L, Psychogios A, Erwin AL, Grebe T, Retterer K, Juusola J
Am J Med Genet A 2018 Sep;176(9):1845-1851. Epub 2018 Jul 28 doi: 10.1002/ajmg.a.40368. PMID: 30055086
Mumtaz S, Yıldız E, Jabeen S, Khan A, Tolun A, Malik S
Am J Med Genet A 2015 Dec;167A(12):3148-52. Epub 2015 Sep 3 doi: 10.1002/ajmg.a.37299. PMID: 26333564
Bassett JH, Boyde A, Zikmund T, Evans H, Croucher PI, Zhu X, Park JW, Cheng SY, Williams GR
Endocrinology 2014 Sep;155(9):3699-712. Epub 2014 Jun 10 doi: 10.1210/en.2013-2156. PMID: 24914936Free PMC Article
Axelrad ME, Glidden R, Nicholson L, Gripp KW
Am J Med Genet A 2004 Aug 1;128A(4):396-400. doi: 10.1002/ajmg.a.30140. PMID: 15264285

Clinical prediction guides

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
Stoll C, Alembik Y, Dott B, Roth MP
Eur J Med Genet 2022 Nov;65(11):104612. Epub 2022 Sep 20 doi: 10.1016/j.ejmg.2022.104612. PMID: 36150686
Gregor A, Sadleir LG, Asadollahi R, Azzarello-Burri S, Battaglia A, Ousager LB, Boonsawat P, Bruel AL, Buchert R, Calpena E, Cogné B, Dallapiccola B, Distelmaier F, Elmslie F, Faivre L, Haack TB, Harrison V, Henderson A, Hunt D, Isidor B, Joset P, Kumada S, Lachmeijer AMA, Lees M, Lynch SA, Martinez F, Matsumoto N, McDougall C, Mefford HC, Miyake N, Myers CT, Moutton S, Nesbitt A, Novelli A, Orellana C, Rauch A, Rosello M, Saida K, Santani AB, Sarkar A, Scheffer IE, Shinawi M, Steindl K, Symonds JD, Zackai EH; University of Washington Center for Mendelian Genomics; DDD Study, Reis A, Sticht H, Zweier C
Am J Hum Genet 2018 Aug 2;103(2):305-316. Epub 2018 Jul 26 doi: 10.1016/j.ajhg.2018.07.003. PMID: 30057029Free PMC Article
Douglas G, Cho MT, Telegrafi A, Winter S, Carmichael J, Zackai EH, Deardorff MA, Harr M, Williams L, Psychogios A, Erwin AL, Grebe T, Retterer K, Juusola J
Am J Med Genet A 2018 Sep;176(9):1845-1851. Epub 2018 Jul 28 doi: 10.1002/ajmg.a.40368. PMID: 30055086
Axelrad ME, Glidden R, Nicholson L, Gripp KW
Am J Med Genet A 2004 Aug 1;128A(4):396-400. doi: 10.1002/ajmg.a.30140. PMID: 15264285

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