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Ruvalcaba syndrome

MedGen UID:
120520
Concept ID:
C0265248
Disease or Syndrome
Synonym: Ruvalcaba Syndrome
SNOMED CT: Ruvalcaba syndrome (3073006)
Modes of inheritance:
Unknown inheritance
MedGen UID:
989040
Concept ID:
CN307042
Finding
Source: Orphanet
Hereditary clinical entity whose mode of inheritance is unknown.
 
Monarch Initiative: MONDO:0008395
OMIM®: 180870
Orphanet: ORPHA3121

Definition

Ruvalcaba syndrome is an extremely rare malformation syndrome, described in less than 10 patients to date, characterized by microcephaly with characteristic facies (downslanting parpebral fissures, microstomia, beaked nose, narrow maxilla), very short stature, narrow thoracic cage with pectus carinatum, hypoplastic genitalia and skeletal anomalies (i.e. characteristic brachydactyly and osteochondritis of the spine) as well as intellectual and developmental delay. [from ORDO]

Clinical features

From HPO
Cryptorchidism
MedGen UID:
8192
Concept ID:
C0010417
Congenital Abnormality
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
Micromelia
MedGen UID:
10031
Concept ID:
C0025995
Congenital Abnormality
The presence of abnormally small extremities.
Small hand
MedGen UID:
108279
Concept ID:
C0575802
Finding
Disproportionately small hand.
Short phalanx of finger
MedGen UID:
163753
Concept ID:
C0877165
Finding
Short (hypoplastic) phalanx of finger, affecting one or more phalanges.
Short metacarpal
MedGen UID:
323064
Concept ID:
C1837084
Anatomical Abnormality
Diminished length of one or more metacarpal bones in relation to the others of the same hand or to the contralateral metacarpal.
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 metatarsal
MedGen UID:
341358
Concept ID:
C1849020
Finding
Diminished length of a metatarsal bone, with resultant proximal displacement of the associated toe.
Limited elbow extension
MedGen UID:
401158
Concept ID:
C1867103
Finding
Limited ability to straighten the arm at the elbow joint.
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).
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.
Inguinal hernia
MedGen UID:
6817
Concept ID:
C0019294
Finding
Protrusion of the contents of the abdominal cavity through the inguinal canal.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Exaggerated anterior convexity of the thoracic vertebral column.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Narrow chest
MedGen UID:
96528
Concept ID:
C0426790
Finding
Reduced width of the chest from side to side, associated with a reduced distance from the sternal notch to the tip of the shoulder.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Dental crowding
MedGen UID:
11850
Concept ID:
C0040433
Finding
Changes in alignment of teeth in the dental arch
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.
Narrow nose
MedGen UID:
98086
Concept ID:
C0426422
Finding
Interalar distance more than 2 SD below the mean for age, or alternatively, an apparently decreased width of the nasal base and alae.
Underdeveloped nasal alae
MedGen UID:
322332
Concept ID:
C1834055
Congenital Abnormality
Thinned, deficient, or excessively arched ala nasi.
Delayed puberty
MedGen UID:
46203
Concept ID:
C0034012
Pathologic Function
Passing the age when puberty normally occurs with no physical or hormonal signs of the onset of puberty.
Abnormality of the breast
MedGen UID:
871338
Concept ID:
C4025829
Anatomical Abnormality
An abnormality of the breast.
Retinal dystrophy
MedGen UID:
208903
Concept ID:
C0854723
Finding
Retinal dystrophy is an abnormality of the retina associated with a hereditary process. Retinal dystrophies are defined by their predominantly monogenic inheritance and they are frequently associated with loss or dysfunction of photoreceptor cells as a primary or secondary event.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVRuvalcaba syndrome
Follow this link to review classifications for Ruvalcaba syndrome in Orphanet.

Professional guidelines

PubMed

Boland CR, Idos GE, Durno C, Giardiello FM, Anderson JC, Burke CA, Dominitz JA, Gross S, Gupta S, Jacobson BC, Patel SG, Shaukat A, Syngal S, Robertson DJ
Gastroenterology 2022 Jun;162(7):2063-2085. Epub 2022 Apr 26 doi: 10.1053/j.gastro.2022.02.021. PMID: 35487791
Boland CR, Idos GE, Durno C, Giardiello FM, Anderson JC, Burke CA, Dominitz JA, Gross S, Gupta S, Jacobson BC, Patel SG, Shaukat A, Syngal S, Robertson DJ
Gastrointest Endosc 2022 Jun;95(6):1025-1047. Epub 2022 Apr 26 doi: 10.1016/j.gie.2022.02.044. PMID: 35487765
Boland CR, Idos GE, Durno C, Giardiello FM, Anderson JC, Burke CA, Dominitz JA, Gross S, Gupta S, Jacobson BC, Patel SG, Shaukat A, Syngal S, Robertson DJ
Am J Gastroenterol 2022 Jun 1;117(6):846-864. Epub 2022 Apr 26 doi: 10.14309/ajg.0000000000001755. PMID: 35471415

Recent clinical studies

Etiology

Yehia L, Keel E, Eng C
Annu Rev Med 2020 Jan 27;71:103-116. Epub 2019 Aug 21 doi: 10.1146/annurev-med-052218-125823. PMID: 31433956
Yehia L, Ni Y, Sesock K, Niazi F, Fletcher B, Chen HJL, LaFramboise T, Eng C
PLoS Genet 2018 Apr;14(4):e1007352. Epub 2018 Apr 23 doi: 10.1371/journal.pgen.1007352. PMID: 29684080Free PMC Article
Mester J, Charis E
Handb Clin Neurol 2015;132:129-37. doi: 10.1016/B978-0-444-62702-5.00009-3. PMID: 26564076
Tan MH, Mester J, Peterson C, Yang Y, Chen JL, Rybicki LA, Milas K, Pederson H, Remzi B, Orloff MS, Eng C
Am J Hum Genet 2011 Jan 7;88(1):42-56. Epub 2010 Dec 30 doi: 10.1016/j.ajhg.2010.11.013. PMID: 21194675Free PMC Article
Gustafson S, Zbuk KM, Scacheri C, Eng C
Semin Oncol 2007 Oct;34(5):428-34. doi: 10.1053/j.seminoncol.2007.07.009. PMID: 17920899

Diagnosis

Duarte M, Milikowski C
Pathology 2022 Mar;54(2):157-166. Epub 2021 Nov 9 doi: 10.1016/j.pathol.2021.08.009. PMID: 34763900
Yehia L, Keel E, Eng C
Annu Rev Med 2020 Jan 27;71:103-116. Epub 2019 Aug 21 doi: 10.1146/annurev-med-052218-125823. PMID: 31433956
Ghusayni R, Sachdev M, Gallentine W, Mikati MA, McDonald MT
Epileptic Disord 2018 Feb 1;20(1):30-34. doi: 10.1684/epd.2018.0954. PMID: 29444762
Mester J, Charis E
Handb Clin Neurol 2015;132:129-37. doi: 10.1016/B978-0-444-62702-5.00009-3. PMID: 26564076
Tan MH, Mester J, Peterson C, Yang Y, Chen JL, Rybicki LA, Milas K, Pederson H, Remzi B, Orloff MS, Eng C
Am J Hum Genet 2011 Jan 7;88(1):42-56. Epub 2010 Dec 30 doi: 10.1016/j.ajhg.2010.11.013. PMID: 21194675Free PMC Article

Therapy

Şahin GE, Hoşnut FÖ, Yeşil Ş, Lafcı NG, Gül AE, Şahin G
Turk J Pediatr 2022;64(4):766-774. doi: 10.24953/turkjped.2021.5330. PMID: 36082652
Bevacqua M, Baldo F, Pastore S, Valencic E, Tommasini A, Maestro A, Rabusin M, Arbo A, Barbi E
Paediatr Drugs 2019 Jun;21(3):185-193. doi: 10.1007/s40272-019-00337-7. PMID: 31124053
Moon K, Ducruet AF, Crowley RW, Klas K, Bristol R, Albuquerque FC
J Neurosurg Pediatr 2013 Jul;12(1):87-92. Epub 2013 May 10 doi: 10.3171/2013.3.PEDS12551. PMID: 23662932
Faisal Ahmed S, Marsh DJ, Weremowicz S, Morton CC, Williams DM, Eng C
J Clin Endocrinol Metab 1999 Dec;84(12):4665-70. doi: 10.1210/jcem.84.12.6178. PMID: 10599735

Prognosis

Yehia L, Keel E, Eng C
Annu Rev Med 2020 Jan 27;71:103-116. Epub 2019 Aug 21 doi: 10.1146/annurev-med-052218-125823. PMID: 31433956
Ngeow J, Sesock K, Eng C
Breast Cancer Res Treat 2017 Aug;165(1):1-8. Epub 2015 Dec 23 doi: 10.1007/s10549-015-3665-z. PMID: 26700035
Stanich PP, Pilarski R, Rock J, Frankel WL, El-Dika S, Meyer MM
World J Gastroenterol 2014 Feb 21;20(7):1833-8. doi: 10.3748/wjg.v20.i7.1833. PMID: 24587660Free PMC Article
Tan MH, Mester J, Peterson C, Yang Y, Chen JL, Rybicki LA, Milas K, Pederson H, Remzi B, Orloff MS, Eng C
Am J Hum Genet 2011 Jan 7;88(1):42-56. Epub 2010 Dec 30 doi: 10.1016/j.ajhg.2010.11.013. PMID: 21194675Free PMC Article
Perriard J, Saurat JH, Harms M
J Am Acad Dermatol 2000 Feb;42(2 Pt 2):348-50. doi: 10.1016/s0190-9622(00)90109-9. PMID: 10640930

Clinical prediction guides

Ghusayni R, Sachdev M, Gallentine W, Mikati MA, McDonald MT
Epileptic Disord 2018 Feb 1;20(1):30-34. doi: 10.1684/epd.2018.0954. PMID: 29444762
Ngeow J, Sesock K, Eng C
Breast Cancer Res Treat 2017 Aug;165(1):1-8. Epub 2015 Dec 23 doi: 10.1007/s10549-015-3665-z. PMID: 26700035
Pilarski R, Stephens JA, Noss R, Fisher JL, Prior TW
J Med Genet 2011 Aug;48(8):505-12. Epub 2011 Jun 9 doi: 10.1136/jmg.2011.088807. PMID: 21659347
Tan MH, Mester J, Peterson C, Yang Y, Chen JL, Rybicki LA, Milas K, Pederson H, Remzi B, Orloff MS, Eng C
Am J Hum Genet 2011 Jan 7;88(1):42-56. Epub 2010 Dec 30 doi: 10.1016/j.ajhg.2010.11.013. PMID: 21194675Free PMC Article
Bonneau D, Longy M
Hum Mutat 2000;16(2):109-22. doi: 10.1002/1098-1004(200008)16:2<109::AID-HUMU3>3.0.CO;2-0. PMID: 10923032

Recent systematic reviews

Kapačinskaitė M, Stratica N, Adomaitienė I, Rascon J, Vaišnytė B
Sci Rep 2024 Sep 10;14(1):21119. doi: 10.1038/s41598-024-71991-2. PMID: 39256443Free PMC Article
Stanich PP, Pilarski R, Rock J, Frankel WL, El-Dika S, Meyer MM
World J Gastroenterol 2014 Feb 21;20(7):1833-8. doi: 10.3748/wjg.v20.i7.1833. PMID: 24587660Free PMC Article

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