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Ventriculomegaly and arthrogryposis(VENARG)

MedGen UID:
1794183
Concept ID:
C5561973
Disease or Syndrome
Synonyms: VENARG; VENTRICULOMEGALY AND ARTHROGRYPOSIS
 
Gene (location): KIDINS220 (2p25.1)
 
Monarch Initiative: MONDO:0859184
OMIM®: 619501

Definition

Ventriculomegaly and arthrogryposis (VENARG) is a severe autosomal recessive congenital disorder characterized by the onset of features in utero that are not compatible with life. Affected pregnancies are terminated spontaneously or by plan due to the severity of the defects. Prenatal ultrasound and autopsy show limb contractures consistent with arthrogryposis and enlarged brain ventricles that may be associated with hydrocephalus, abnormalities of the corpus callosum, and cerebellar hypoplasia. Some affected fetuses may also have congenital heart disease and hydrops fetalis (summary by Mero et al., 2017 and El-Dessouky et al., 2020). [from OMIM]

Clinical features

From HPO
Clubfoot
MedGen UID:
3130
Concept ID:
C0009081
Congenital Abnormality
Clubfoot is a congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities (Cardy et al., 2007). Clubfoot may occur in isolation or as part of a syndrome (e.g., diastrophic dysplasia, 222600). Clubfoot has been reported with deficiency of long bones and mirror-image polydactyly (Gurnett et al., 2008; Klopocki et al., 2012).
Ulnar deviation of the wrist
MedGen UID:
115906
Concept ID:
C0231678
Sign or Symptom
Hand clenching
MedGen UID:
65994
Concept ID:
C0239815
Finding
An abnormal hand posture in which the hands are clenched to fists. All digits held completely flexed at the metacarpophalangeal and interphalangeal joints. In prenatal sonography of the fetal clenched hand, the index finger overlaps a clenched fist formed by the other digits. The proximal interphalangeal articulation of the index finger is flexed and ulnarly deviated, and the thumb is adducted.
Corpus callosum, agenesis of
MedGen UID:
104498
Concept ID:
C0175754
Congenital Abnormality
The corpus callosum is the largest fiber tract in the central nervous system and the major interhemispheric fiber bundle in the brain. Formation of the corpus callosum begins as early as 6 weeks' gestation, with the first fibers crossing the midline at 11 to 12 weeks' gestation, and completion of the basic shape by age 18 to 20 weeks (Schell-Apacik et al., 2008). Agenesis of the corpus callosum (ACC) is one of the most frequent malformations in brain with a reported incidence ranging between 0.5 and 70 in 10,000 births. ACC is a clinically and genetically heterogeneous condition, which can be observed either as an isolated condition or as a manifestation in the context of a congenital syndrome (see MOLECULAR GENETICS and Dobyns, 1996). Also see mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; 157600). Schell-Apacik et al. (2008) noted that there is confusion in the literature regarding radiologic terminology concerning partial absence of the corpus callosum, where various designations have been used, including hypogenesis, hypoplasia, partial agenesis, or dysgenesis.
Cerebellar hypoplasia
MedGen UID:
120578
Concept ID:
C0266470
Congenital Abnormality
Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Arthrogryposis multiplex congenita
MedGen UID:
1830310
Concept ID:
C5779613
Disease or Syndrome
Multiple congenital contractures in different body areas.

Professional guidelines

PubMed

Drury S, Boustred C, Tekman M, Stanescu H, Kleta R, Lench N, Chitty LS, Scott RH
Am J Med Genet A 2014 Jul;164A(7):1777-83. Epub 2014 Apr 3 doi: 10.1002/ajmg.a.36506. PMID: 24700531
Cherian L, Rosenberg JJ
Pediatr Rev 2010 Sep;31(9):385-7. doi: 10.1542/pir.31-9-385. PMID: 20810705

Recent clinical studies

Etiology

Gregory LC, Shah P, Sanner JRF, Arancibia M, Hurst J, Jones WD, Spoudeas H, Le Quesne Stabej P, Williams HJ, Ocaka LA, Loureiro C, Martinez-Aguayo A, Dattani MT
J Clin Endocrinol Metab 2019 Dec 1;104(12):5737-5750. doi: 10.1210/jc.2019-00631. PMID: 31504653Free PMC Article
Sejvar JJ
Continuum (Minneap Minn) 2018 Oct;24(5, Neuroinfectious Disease):1512-1534. doi: 10.1212/CON.0000000000000652. PMID: 30273250
Melo AS, Aguiar RS, Amorim MM, Arruda MB, Melo FO, Ribeiro ST, Batista AG, Ferreira T, Dos Santos MP, Sampaio VV, Moura SR, Rabello LP, Gonzaga CE, Malinger G, Ximenes R, de Oliveira-Szejnfeld PS, Tovar-Moll F, Chimelli L, Silveira PP, Delvechio R, Higa L, Campanati L, Nogueira RM, Filippis AM, Szejnfeld J, Voloch CM, Ferreira OC Jr, Brindeiro RM, Tanuri A
JAMA Neurol 2016 Dec 1;73(12):1407-1416. doi: 10.1001/jamaneurol.2016.3720. PMID: 27695855
van der Linden V, Filho EL, Lins OG, van der Linden A, Aragão Mde F, Brainer-Lima AM, Cruz DD, Rocha MA, Sobral da Silva PF, Carvalho MD, do Amaral FJ, Gomes JA, Ribeiro de Medeiros IC, Ventura CV, Ramos RC
BMJ 2016 Aug 9;354:i3899. doi: 10.1136/bmj.i3899. PMID: 27509902Free PMC Article
Schaaf CP, Koster J, Katsonis P, Kratz L, Shchelochkov OA, Scaglia F, Kelley RI, Lichtarge O, Waterham HR, Shinawi M
Am J Med Genet A 2011 Jul;155A(7):1597-604. Epub 2011 Jun 10 doi: 10.1002/ajmg.a.34040. PMID: 21671375Free PMC Article

Diagnosis

Seidahmed MZ, Maddirevula S, Miqdad AM, Al Faifi A, Al Samadi A, Alkuraya FS
Am J Med Genet A 2021 Mar;185(3):945-948. Epub 2020 Dec 27 doi: 10.1002/ajmg.a.62052. PMID: 33369052
Freitas DA, Souza-Santos R, Carvalho LMA, Barros WB, Neves LM, Brasil P, Wakimoto MD
PLoS One 2020;15(12):e0242367. Epub 2020 Dec 15 doi: 10.1371/journal.pone.0242367. PMID: 33320867Free PMC Article
Sejvar JJ
Continuum (Minneap Minn) 2018 Oct;24(5, Neuroinfectious Disease):1512-1534. doi: 10.1212/CON.0000000000000652. PMID: 30273250
van der Linden V, Filho EL, Lins OG, van der Linden A, Aragão Mde F, Brainer-Lima AM, Cruz DD, Rocha MA, Sobral da Silva PF, Carvalho MD, do Amaral FJ, Gomes JA, Ribeiro de Medeiros IC, Ventura CV, Ramos RC
BMJ 2016 Aug 9;354:i3899. doi: 10.1136/bmj.i3899. PMID: 27509902Free PMC Article
Ramieri V, Tarani L, Costantino F, Basile E, Liberati N, Rinna C, Cascone P, Colloridi F
J Craniofac Surg 2011 Nov;22(6):2124-8. doi: 10.1097/SCS.0b013e3182323cdf. PMID: 22067867

Therapy

Orioli IM, Castilla EE
BJOG 2000 Apr;107(4):519-23. doi: 10.1111/j.1471-0528.2000.tb13272.x. PMID: 10759272
Gonzalez CH, Marques-Dias MJ, Kim CA, Sugayama SM, Da Paz JA, Huson SM, Holmes LB
Lancet 1998 May 30;351(9116):1624-7. doi: 10.1016/S0140-6736(97)12363-7. PMID: 9620717
Spranger JW, Schinzel A, Myers T, Ryan J, Giedion A, Opitz JM
Am J Med Genet 1980;5(1):13-24. doi: 10.1002/ajmg.1320050104. PMID: 7395897

Prognosis

Melo A, de Sales Tavares J, de Assis Costa M, Santana de Aguiar R, Malinger G, de Oliveira Melo F, Balbino da-Silva M, Luiz Fonseca Schamber-Reis B, Gama G, Tanuri A, Chimelli L, Oliveira-Szejnfeld P, M Ramos de Amorim M
Prenat Diagn 2020 Dec;40(13):1732-1740. Epub 2020 Oct 27 doi: 10.1002/pd.5831. PMID: 32939752
Zare Mehrjardi M, Poretti A, Huisman TA, Werner H, Keshavarz E, Araujo Júnior E
Jpn J Radiol 2017 Mar;35(3):89-94. Epub 2017 Jan 10 doi: 10.1007/s11604-016-0609-4. PMID: 28074379
Sarno M, Aquino M, Pimentel K, Cabral R, Costa G, Bastos F, Brites C
Ultrasound Obstet Gynecol 2017 Dec;50(6):717-722. Epub 2017 Nov 8 doi: 10.1002/uog.17303. PMID: 27644020
Melo AS, Aguiar RS, Amorim MM, Arruda MB, Melo FO, Ribeiro ST, Batista AG, Ferreira T, Dos Santos MP, Sampaio VV, Moura SR, Rabello LP, Gonzaga CE, Malinger G, Ximenes R, de Oliveira-Szejnfeld PS, Tovar-Moll F, Chimelli L, Silveira PP, Delvechio R, Higa L, Campanati L, Nogueira RM, Filippis AM, Szejnfeld J, Voloch CM, Ferreira OC Jr, Brindeiro RM, Tanuri A
JAMA Neurol 2016 Dec 1;73(12):1407-1416. doi: 10.1001/jamaneurol.2016.3720. PMID: 27695855
Ramieri V, Tarani L, Costantino F, Basile E, Liberati N, Rinna C, Cascone P, Colloridi F
J Craniofac Surg 2011 Nov;22(6):2124-8. doi: 10.1097/SCS.0b013e3182323cdf. PMID: 22067867

Clinical prediction guides

Yilmaz Gulec E, Turgut GT, Gezdirici A, Karaman V, Ozturk FN, Avci S, Kalayci T, Senturk L, Ayaz A, Kayserili H, Uyguner ZO, Altunoğlu U
Clin Genet 2022 Sep;102(3):201-217. Epub 2022 Jul 12 doi: 10.1111/cge.14177. PMID: 35699517
Gregory LC, Shah P, Sanner JRF, Arancibia M, Hurst J, Jones WD, Spoudeas H, Le Quesne Stabej P, Williams HJ, Ocaka LA, Loureiro C, Martinez-Aguayo A, Dattani MT
J Clin Endocrinol Metab 2019 Dec 1;104(12):5737-5750. doi: 10.1210/jc.2019-00631. PMID: 31504653Free PMC Article
Sejvar JJ
Continuum (Minneap Minn) 2018 Oct;24(5, Neuroinfectious Disease):1512-1534. doi: 10.1212/CON.0000000000000652. PMID: 30273250
Chimelli L, Avvad-Portari E
Childs Nerv Syst 2018 Jan;34(1):95-99. Epub 2017 Nov 22 doi: 10.1007/s00381-017-3651-3. PMID: 29167994
van der Linden V, Filho EL, Lins OG, van der Linden A, Aragão Mde F, Brainer-Lima AM, Cruz DD, Rocha MA, Sobral da Silva PF, Carvalho MD, do Amaral FJ, Gomes JA, Ribeiro de Medeiros IC, Ventura CV, Ramos RC
BMJ 2016 Aug 9;354:i3899. doi: 10.1136/bmj.i3899. PMID: 27509902Free PMC Article

Recent systematic reviews

Rice SM, Varotsis DF, Wodoslawsky S, Critchlow E, Liu R, McLaren RA Jr, Makhamreh MM, Firman B, Berger SI, Al-Kouatly HB
Prenat Diagn 2024 Oct;44(11):1381-1397. Epub 2024 Sep 3 doi: 10.1002/pd.6637. PMID: 39228063
Freitas DA, Souza-Santos R, Carvalho LMA, Barros WB, Neves LM, Brasil P, Wakimoto MD
PLoS One 2020;15(12):e0242367. Epub 2020 Dec 15 doi: 10.1371/journal.pone.0242367. PMID: 33320867Free PMC Article

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