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Richieri Costa-Pereira syndrome(RCPS)

MedGen UID:
336581
Concept ID:
C1849348
Disease or Syndrome
Synonyms: Richieri-Costa and Pereira form of acrofacial dysostosis; Robin sequence with cleft mandible and limb anomalies; Short stature, Robin sequence, cleft mandible, pre/postaxial hand anomalies, and clubfoot
SNOMED CT: Robin sequence with cleft mandible and limb anomalies syndrome (723998001); Short stature, Pierre Robin sequence, cleft mandible, hand anomalies, clubfoot syndrome (723998001); Richieri Costa Pereira syndrome (723998001)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): EIF4A3 (17q25.3)
 
Monarch Initiative: MONDO:0009998
OMIM®: 268305
Orphanet: ORPHA3102

Definition

Patients with Richieri-Costa-Pereira syndrome display a pattern of anomalies consisting of microstomia, micrognathia, abnormal fusion of the mandible, cleft palate/Robin sequence, absence of lower central incisors, minor ear anomalies, hypoplastic first ray, abnormal tibiae, hypoplastic halluces, and clubfeet. Learning disability is also a common finding (summary by Favaro et al., 2011). [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).
Short thumb
MedGen UID:
98469
Concept ID:
C0431890
Congenital Abnormality
Hypoplasia (congenital reduction in size) of the thumb.
Hip subluxation
MedGen UID:
140946
Concept ID:
C0434785
Injury or Poisoning
A partial dislocation of the hip joint, whereby the head of the femur is partially displaced from the socket.
Radial deviation of the hand
MedGen UID:
108280
Concept ID:
C0575803
Finding
An abnormal position of the hand in which the wrist is bent toward the radius (i.e., toward the thumb).
Hypoplasia of the radius
MedGen UID:
672334
Concept ID:
C0685381
Congenital Abnormality
Underdevelopment of the radius.
Short phalanx of finger
MedGen UID:
163753
Concept ID:
C0877165
Finding
Short (hypoplastic) phalanx of finger, affecting one or more phalanges.
Acetabular dysplasia
MedGen UID:
233069
Concept ID:
C1328407
Anatomical Abnormality
A smaller than normal acetabulum that has insufficient femoral head coverage leading to abnormal hip joint contact pressures, instability and pain.
Fibular hypoplasia
MedGen UID:
316909
Concept ID:
C1832119
Finding
Underdevelopment of the fibula.
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 5th finger
MedGen UID:
334269
Concept ID:
C1842878
Congenital Abnormality
Hypoplasia (congenital reduction in size) of the fifth finger, also known as the little finger.
Small thenar eminence
MedGen UID:
335432
Concept ID:
C1846474
Finding
Underdevelopment of the thenar eminence with reduced palmar soft tissue mass surrounding the base of the thumb.
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).
Short tibia
MedGen UID:
338005
Concept ID:
C1850259
Finding
Underdevelopment (reduced size) of the tibia.
4-5 metacarpal synostosis
MedGen UID:
395341
Concept ID:
C1859768
Anatomical Abnormality
Small hypothenar eminence
MedGen UID:
396124
Concept ID:
C1861395
Finding
Reduced muscle mass on the ulnar side of the palm, that is, reduction in size of the hypothenar eminence.
Mesomelic arm shortening
MedGen UID:
350587
Concept ID:
C1862087
Finding
Shortening of the middle parts of the arm in relation to the upper and terminal segments.
Proximal placement of thumb
MedGen UID:
356033
Concept ID:
C1865572
Finding
Proximal mislocalization of the thumb.
Short hallux
MedGen UID:
400890
Concept ID:
C1865992
Finding
Underdevelopment (hypoplasia) of the big toe.
Mesomelic leg shortening
MedGen UID:
369436
Concept ID:
C1969178
Finding
Shortening of the middle parts of the leg in relation to the upper and terminal segments.
Tibial deviation of toes
MedGen UID:
812863
Concept ID:
C3806533
Finding
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).
Feeding difficulties
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Protruding ear
MedGen UID:
343309
Concept ID:
C1855285
Finding
Angle formed by the plane of the ear and the mastoid bone greater than the 97th centile for age (objective); or, outer edge of the helix more than 2 cm from the mastoid at the point of maximum distance (objective).
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.
Hip dislocation
MedGen UID:
42455
Concept ID:
C0019554
Injury or Poisoning
Displacement of the femur from its normal location in the hip joint.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Cleft mandible
MedGen UID:
146346
Concept ID:
C0685786
Finding
Midline deficiency of the mandible and some or all overlying tissues.
Microretrognathia
MedGen UID:
326907
Concept ID:
C1839546
Finding
A form of developmental hypoplasia of the mandible in which the mandible is mislocalised posteriorly.
Abnormal aryepiglottic fold morphology
MedGen UID:
340304
Concept ID:
C1849357
Anatomical Abnormality
An abnormality of the aryepiglottic fold.
Aplasia of the epiglottis
MedGen UID:
870194
Concept ID:
C4024628
Finding
Absence of the epiglottis.
Abnormality of the voice
MedGen UID:
867406
Concept ID:
C4021776
Finding
Narrow mouth
MedGen UID:
44435
Concept ID:
C0026034
Congenital Abnormality
Distance between the commissures of the mouth more than 2 SD below the mean. Alternatively, an apparently decreased width of the oral aperture (subjective).
Isolated Pierre-Robin syndrome
MedGen UID:
19310
Concept ID:
C0031900
Congenital Abnormality
Pierre Robin sequence is a craniofacial anomaly comprising mandibular hypoplasia, cleft secondary palate, and glossoptosis leading to life-threatening obstructive apnea and feeding difficulties during the neonatal period (summary by Tan et al., 2013).
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Prominent nose
MedGen UID:
98423
Concept ID:
C0426415
Finding
Distance between subnasale and pronasale more than two standard deviations above the mean, or alternatively, an apparently increased anterior protrusion of the nasal tip.
Cleft lower alveolar ridge
MedGen UID:
336582
Concept ID:
C1849350
Finding
Cleft palate
MedGen UID:
756015
Concept ID:
C2981150
Congenital Abnormality
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).
Agenesis of mandibular central incisor
MedGen UID:
870605
Concept ID:
C4025054
Anatomical Abnormality
Agenesis of lower secondary incisor or lower primary incisor.
Bifid uvula
MedGen UID:
1646931
Concept ID:
C4551488
Congenital Abnormality
Uvula separated into two parts most easily seen at the tip.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVRichieri Costa-Pereira syndrome
Follow this link to review classifications for Richieri Costa-Pereira syndrome in Orphanet.

Recent clinical studies

Etiology

Pardo MP, Santos GLD, Carvalho IMM, Tjioe KC
Cleft Palate Craniofac J 2021 Nov;58(11):1370-1375. Epub 2021 Jan 28 doi: 10.1177/1055665620987749. PMID: 33504197
Pinto RO, Peixoto AP, Pinto ADS, Richieri-Costa A, Raveli DB, Tonello C, Dalben GDS
J Craniofac Surg 2020 Jun;31(4):e356-e359. doi: 10.1097/SCS.0000000000006338. PMID: 32217860
Pinto RO, Peixoto AP, Pinto ADS, Richieri-Costa A, Zechi-Ceide RM, Ozawa TO, Dalben GDS
J Craniofac Surg 2018 Sep;29(6):1596-1600. doi: 10.1097/SCS.0000000000004588. PMID: 29863549

Diagnosis

Lehalle D, Wieczorek D, Zechi-Ceide RM, Passos-Bueno MR, Lyonnet S, Amiel J, Gordon CT
Clin Genet 2015 Nov;88(5):405-15. Epub 2015 May 1 doi: 10.1111/cge.12596. PMID: 25865758
Severini JM, da Silva Dalben G, Richieri-Costa A, Ozawa TO
Oral Surg Oral Med Oral Pathol Oral Radiol 2012 Jul;114(1):99-106. doi: 10.1016/j.oooo.2012.03.009. PMID: 22727098
Souza J, dal Vesco K, Tonocchi R, Closs-Ono MC, Passos-Bueno MR, da Silva-Freitas R
Am J Med Genet A 2011 May;155A(5):1173-7. Epub 2011 Apr 11 doi: 10.1002/ajmg.a.33975. PMID: 21485002

Therapy

Pinto RO, Peixoto AP, Pinto ADS, Richieri-Costa A, Zechi-Ceide RM, Ozawa TO, Dalben GDS
J Craniofac Surg 2018 Sep;29(6):1596-1600. doi: 10.1097/SCS.0000000000004588. PMID: 29863549

Clinical prediction guides

Pardo MP, Santos GLD, Carvalho IMM, Tjioe KC
Cleft Palate Craniofac J 2021 Nov;58(11):1370-1375. Epub 2021 Jan 28 doi: 10.1177/1055665620987749. PMID: 33504197
Bertola DR, Hsia G, Alvizi L, Gardham A, Wakeling EL, Yamamoto GL, Honjo RS, Oliveira LAN, Di Francesco RC, Perez BA, Kim CA, Passos-Bueno MR
Clin Genet 2018 Apr;93(4):800-811. Epub 2018 Feb 20 doi: 10.1111/cge.13169. PMID: 29112243
Severini JM, da Silva Dalben G, Richieri-Costa A, Ozawa TO
Oral Surg Oral Med Oral Pathol Oral Radiol 2012 Jul;114(1):99-106. doi: 10.1016/j.oooo.2012.03.009. PMID: 22727098
Miguel HC, Carneiro CG, Tabith A Jr, Zechi-Ceide RM, Genaro KF
Am J Med Genet A 2012 Aug;158A(8):1967-70. Epub 2012 Jun 18 doi: 10.1002/ajmg.a.35421. PMID: 22711187
Favaro FP, Zechi-Ceide RM, Alvarez CW, Maximino LP, Antunes LF, Richieri-Costa A, Guion-Almeida ML
Am J Med Genet A 2011 Feb;155A(2):322-31. Epub 2010 Dec 22 doi: 10.1002/ajmg.a.33806. PMID: 21271648

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