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Autosomal recessive amelia(PAPPAS)

MedGen UID:
321955
•Concept ID:
C1832432
•
Disease or Syndrome
Synonym: Amelia, Autosomal Recessive
SNOMED CT: Autosomal recessive amelia (726735000)
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).
Autosomal recessive inheritance (Orphanet)
 
Gene (location): TBX4 (17q23.2)
 
Monarch Initiative: MONDO:0011054
OMIM®: 601360
Orphanet: ORPHA1027

Definition

Posterior amelia with pelvic and pulmonary hypoplasia syndrome (PAPPAS) is characterized by absent lower limbs, severely hypoplastic or absent pelvic bones, and hypoplasia of the sacrum, as well as hypoplasia of the lungs with pulmonary segmentation defect. Ambiguous genitalia have also been observed (Kariminejad et al., 2019). Heterozygous mutation in the TBX4 gene causes ischiocoxopodopatellar syndrome with or without pulmonary arterial hypertension (ICPPS; 147891). [from OMIM]

Clinical features

From HPO
Amelia
MedGen UID:
8014
•Concept ID:
C0002447
•
Congenital Abnormality
Congenital absence (aplasia) of one or more limbs.
See: Feature record | Search on this feature

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAutosomal recessive amelia
Follow this link to review classifications for Autosomal recessive amelia in Orphanet.

Professional guidelines

PubMed

ROBERTS SYNDROME: CLINICAL AND CYTOGENETIC STUDIES IN 8 EGYPTIAN PATIENTS AND MOLECULAR STUDIES IN 4 PATIENTS WITH GENOTYPE/PHENOTYPE CORRELATION.
Ismail S, Essawi M, Sedky N, Hassan H, Fayez A, Helmy N, Shehab M, Farouk D, Elruby M, Otaify G, Eldarsh A, Hosny L, Gaber K, Aboul-Ezz EHA, Ramzy MI, Mehrez MI, Hassib NF, Elhadidi SMA, Aglan MS, Temtamy SA
Genet Couns 2016;27(3):305-323. PMID: 30204960
Inactivating mutations in ESCO2 cause SC phocomelia and Roberts syndrome: no phenotype-genotype correlation.
Schüle B, Oviedo A, Johnston K, Pai S, Francke U
Am J Hum Genet 2005 Dec;77(6):1117-28. Epub 2005 Oct 31 doi: 10.1086/498695. PMID: 16380922Free PMC Article

Recent clinical studies

Etiology

Multidisciplinary approach to patients with manifestations and pulmonary complications of cystic fibrosis.
Biciuşcă V, Petrescu IO, Singer CE, Oancea AG, Petrescu AM, Stan IS, Durand P, Taisescu CI, Dumitrescu D, Dobrescu MA, Udriştoiu I, Tudoraşcu DR, Petrescu F
Rom J Morphol Embryol 2020 Apr-Jun;61(2):397-406. doi: 10.47162/RJME.61.2.09. PMID: 33544791Free PMC Article
The Roberts syndrome: a case report of an infant with valvular aortic stenosis and mutation in ESCO2.
Dogan M, Firinci F, Balci YI, Zeybek S, Ozgürler F, Erdogan I, Varan B, Semerci CN
J Pak Med Assoc 2014 Apr;64(4):457-60. PMID: 24864645
Femorotibial ankylosis in a child with Roberts syndrome: an "aggressive" approach to habilitation.
Eylon S, Beeri M, Joseph K, Meyer S
J Pediatr Orthop 2007 Dec;27(8):926-9. doi: 10.1097/bpo.0b013e31815a6045. PMID: 18209617
von Voss-Cherstvoy syndrome: a variable perinatally lethal syndrome of multiple congenital anomalies.
Lubinsky MS, Kahler SG, Speer IE, Hoyme HE, Kirillova IA, Lurie IW
Am J Med Genet 1994 Sep 1;52(3):272-8. doi: 10.1002/ajmg.1320520305. PMID: 7810558
Genetics and limb deficiencies.
Lenz W
Clin Orthop Relat Res 1980 May;(148):9-17. PMID: 7379414

Diagnosis

Molecular basis of mucopolysaccharidosis IVA (Morquio A syndrome): A review and classification of GALNS gene variants and reporting of 68 novel variants.
Zanetti A, D'Avanzo F, AlSayed M, Brusius-Facchin AC, Chien YH, Giugliani R, Izzo E, Kasper DC, Lin HY, Lin SP, Pollard L, Singh A, Tonin R, Wood T, Morrone A, Tomanin R
Hum Mutat 2021 Nov;42(11):1384-1398. Epub 2021 Aug 23 doi: 10.1002/humu.24270. PMID: 34387910Free PMC Article
PRDX1 gene-related epi-cblC disease is a common type of inborn error of cobalamin metabolism with mono- or bi-allelic MMACHC epimutations.
Cavicchi C, Oussalah A, Falliano S, Ferri L, Gozzini A, Gasperini S, Motta S, Rigoldi M, Parenti G, Tummolo A, Meli C, Menni F, Furlan F, Daniotti M, Malvagia S, la Marca G, Chery C, Morange PE, Tregouet D, Donati MA, Guerrini R, Guéant JL, Morrone A
Clin Epigenetics 2021 Jul 2;13(1):137. doi: 10.1186/s13148-021-01117-2. PMID: 34215320Free PMC Article
Multidisciplinary approach to patients with manifestations and pulmonary complications of cystic fibrosis.
Biciuşcă V, Petrescu IO, Singer CE, Oancea AG, Petrescu AM, Stan IS, Durand P, Taisescu CI, Dumitrescu D, Dobrescu MA, Udriştoiu I, Tudoraşcu DR, Petrescu F
Rom J Morphol Embryol 2020 Apr-Jun;61(2):397-406. doi: 10.47162/RJME.61.2.09. PMID: 33544791Free PMC Article
Type I sialidosis, a normosomatic lysosomal disease, in the differential diagnosis of late-onset ataxia and myoclonus: An overview.
Caciotti A, Melani F, Tonin R, Cellai L, Catarzi S, Procopio E, Chilleri C, Mavridou I, Michelakakis H, Fioravanti A, d'Azzo A, Guerrini R, Morrone A
Mol Genet Metab 2020 Feb;129(2):47-58. Epub 2019 Oct 31 doi: 10.1016/j.ymgme.2019.09.005. PMID: 31711734
Tetra-amelia and lung hypo/aplasia syndrome: new case report and review.
Sousa SB, Pina R, Ramos L, Pereira N, Krahn M, Borozdin W, Kohlhase J, Amorim M, Gonnet K, Lévy N, Carreira IM, Couceiro AB, Saraiva JM
Am J Med Genet A 2008 Nov 1;146A(21):2799-803. doi: 10.1002/ajmg.a.32489. PMID: 18837045

Therapy

Real-time measurement of blood pressure with Nexfin in a patient with thalidomide-related phocomelia.
Earle R, Vaghadia H, Shanahan E, Tang R, Sawka A
J Clin Anesth 2016 Nov;34:244-6. Epub 2016 May 13 doi: 10.1016/j.jclinane.2016.04.035. PMID: 27687383
Humeroradial synostosis, ulnar aplasia and oligodactyly, with contralateral amelia, in a child with prenatal cocaine exposure.
Marles SL, Reed M, Evans JA
Am J Med Genet A 2003 Jan 1;116A(1):85-9. doi: 10.1002/ajmg.a.10731. PMID: 12476458

Prognosis

Hypopigmented patches in Roberts/SC phocomelia syndrome occur via aneuploidy susceptibility.
Sezer A, Kayhan G, Zenker M, Percin EF
Eur J Med Genet 2019 Dec;62(12):103608. Epub 2018 Dec 24 doi: 10.1016/j.ejmg.2018.12.013. PMID: 30590172
Intrapartum diagnostic of Roberts syndrome - case presentation.
Socolov RV, Andreescu NI, Haliciu AM, Gorduza EV, Dumitrache F, Balan RA, Puiu M, Dobrescu MA, Socolov DG
Rom J Morphol Embryol 2015;56(2):585-8. PMID: 26193234
Inactivating mutations in ESCO2 cause SC phocomelia and Roberts syndrome: no phenotype-genotype correlation.
Schüle B, Oviedo A, Johnston K, Pai S, Francke U
Am J Hum Genet 2005 Dec;77(6):1117-28. Epub 2005 Oct 31 doi: 10.1086/498695. PMID: 16380922Free PMC Article
Prenatal diagnosis of unilateral tibial hemimelia.
Dreyfus M, Baldauf JJ, Rigaut E, Clavert JM, Gasser B, Ritter J
Ultrasound Obstet Gynecol 1996 Mar;7(3):205-7. doi: 10.1046/j.1469-0705.1996.07030205.x. PMID: 8705415
Severe case of Al Awadi/Raas-Rothschild syndrome or new, possibly autosomal recessive facio-skeleto-genital syndrome.
Mollica F, Mazzone D, Cimino G, Opitz JM
Am J Med Genet 1995 Mar 27;56(2):168-72. doi: 10.1002/ajmg.1320560211. PMID: 7625440

Clinical prediction guides

The molecular mechanism underlying Roberts syndrome involves loss of ESCO2 acetyltransferase activity.
Gordillo M, Vega H, Trainer AH, Hou F, Sakai N, Luque R, Kayserili H, Basaran S, Skovby F, Hennekam RC, Uzielli ML, Schnur RE, Manouvrier S, Chang S, Blair E, Hurst JA, Forzano F, Meins M, Simola KO, Raas-Rothschild A, Schultz RA, McDaniel LD, Ozono K, Inui K, Zou H, Jabs EW
Hum Mol Genet 2008 Jul 15;17(14):2172-80. Epub 2008 Apr 14 doi: 10.1093/hmg/ddn116. PMID: 18411254
Roberts syndrome: study of 4 new Rgyptian cases with comparison of clinical and cytogenetic findings.
Temtamy SA, Ismail S, Helmy NA
Genet Couns 2006;17(1):1-13. PMID: 16719272
Inactivating mutations in ESCO2 cause SC phocomelia and Roberts syndrome: no phenotype-genotype correlation.
Schüle B, Oviedo A, Johnston K, Pai S, Francke U
Am J Hum Genet 2005 Dec;77(6):1117-28. Epub 2005 Oct 31 doi: 10.1086/498695. PMID: 16380922Free PMC Article
Homozygous WNT3 mutation causes tetra-amelia in a large consanguineous family.
Niemann S, Zhao C, Pascu F, Stahl U, Aulepp U, Niswander L, Weber JL, Müller U
Am J Hum Genet 2004 Mar;74(3):558-63. Epub 2004 Feb 5 doi: 10.1086/382196. PMID: 14872406Free PMC Article
A minimalist approach to gene mapping: locating the gene for acheiropodia, by homozygosity analysis.
Escamilla MA, DeMille MC, Benavides E, Roche E, Almasy L, Pittman S, Hauser J, Lew DF, Freimer NB, Whittle MR
Am J Hum Genet 2000 Jun;66(6):1995-2000. Epub 2000 Apr 25 doi: 10.1086/302921. PMID: 10780921Free PMC Article

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