NORD gratefully acknowledges Uta Francke, MD, Department of Genetics, Stanford University School of Medicine, for assistance in the preparation of this report.
The symptoms associated with Roberts syndrome vary widely from case to case even among members of the same family. Most infants experience growth deficiencies and have abnormalities of the limbs and craniofacial region. Infants with Roberts syndrome often experience life-threatening complications early in infancy.
Affected infants may experience growth deficiencies before and after birth (pre- and postnatally). Mental retardation is a variable finding that occurs in approximately 50 percent of cases.
Limb abnormalities are common in infants with Roberts syndrome and may range from underdeveloped bones in the arms and legs (hypomelia) to complete absence of all four limbs (tetraphocomelia). The arms are usually more severely affected than the legs.
Additional abnormalities may affect the arms and legs including permanent fixation (contracture) of various joints, especially the knees and elbows. The number of fingers and/or toes may be reduced and the fifth fingers may be in a fixed laterally deviated position (clinodactyly). Webbing of the finger and toes (syndactyly) may also be present. Infants with Roberts syndrome may also have a form of club foot where the heel of the foot may be elevated and turned outward away from the body (talipes equinovalgus).
Infants with Roberts Syndrome also have a variety of craniofacial abnormalities including a small, broad head (microbrachycephaly); an abnormal groove in the upper lip (cleft lip) with or without incomplete closure of the roof of the mouth (cleft palate); a flattened nose with small wings; an abnormally small jaw (micrognathia); sparse, silvery hair; and malformed, low-set ears that often lack lobes. Some infants may experience premature fusion of the fibrous joints (cranial sutures) between certain bones in the skull (craniosynostosis). Affected infants may have eye (ocular) abnormalities including widely spaced eyes (hypertelorism); unusually small eyes (microphthalmia); cloudy corneas; and bulging or prominent eyes (proptosis) due to shallow eye cavities (orbits). In some cases, the whites of the eyes may be blue (blue sclera) and increased pressure within the eyeball (glaucoma) may also be present.
Some infants with Roberts syndrome may have one or more pink or dark red irregularly shaped patches of skin (hemangiomas) on the face caused by dense collections of small blood vessels (capillaries).
Infants with Roberts syndrome often have abnormalities affecting the genitourinary system. Males may have the urinary opening located on the underside of the penis (hypospadias) and the testicles may fail to descend into the scrotum (cryptorchidism). Females may have a malformed uterus with horn-like branches (bicornuate uterus).
Less common symptoms associated with Roberts syndrome include malformed kidneys, an abnormal increase in cerebrospinal fluid resulting in enlargement of the skull (hydrocephalus), paralysis of cranial nerves, seizures, heart defects and a decreased number of blood platelets (thrombocytopenia).
Roberts syndrome is inherited as an autosomal recessive disorder. Genetic diseases of this type are determined by two abnormal genes, one received from the father and one from the mother.
Recessive genetic disorders occur when an individual inherits an abnormal version of the same gene from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%.
Some cases of Roberts syndrome have had parents who were related by blood (consanguineous). All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
Investigators have determined that Roberts syndrome is caused by disruptions or changes of the ESCO2 (establishment of cohesion 1 homolog 2) gene located on the short arm (p) of chromosome 8 (8p21.1). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Pairs of human chromosomes are numbered from 1 through 22, and an additional 23rd pair of sex chromosomes, which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further subdivided into many regions, bands and sub-bands that are numbered. For example, “chromosome 8p21.1” refers to region 2, band 1, sub-band 1 on the short arm of chromosome 8. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Certain complex chromosomal abnormalities are distinguishing features of Roberts syndrome. Most affected individuals experience premature centromere separation of various chromosomes, especially chromosomes 1, 9, and 16, a phenomenon often referred to as “puffing.” The centromere is the center of a chromosome located between the long and short arms of a chromosome. The characteristic “puffing” abnormality is apparent in mitosis, the process in which a cell divides ultimately forming two cells identical to the original.
Roberts syndrome affects males and females in equal numbers. The incidence of Roberts syndrome is unknown.
A diagnosis of Roberts syndrome is suspected based upon a thorough clinical evaluation, detailed patient history and identification of characteristic abnormalities. A diagnosis may be confirmed by chromosomal analysis that detects characteristic premature centromere separation (puffing) on various chromosomes. Absence of puffing does not exclude the diagnosis, as it was reported to be absent in some clinically diagnosed cases.
In some cases, it is possible that a diagnosis of Roberts syndrome may be suspected before birth (prenatally) based upon specialized tests, such as amniocentesis, chorionic villus sampling (CVS), or ultrasonography. During amniocentesis, a sample of fluid that surrounds the developing fetus is removed and analyzed, while CVS involves the removal of tissue samples from a portion of the placenta. Chromosomal studies performed on such fluid or tissue samples may reveal premature centromere separation (puffing) in meiotic cells. During fetal ultrasonography, reflected sound waves create an image of the developing fetus, potentially revealing certain developmental abnormalities suggestive Roberts syndrome (e.g., limb abnormalities).
The diagnosis of RBS is confirmed by molecular testing for ESCO2 mutations. The presence of mutations in this gene is strictly correlated with the centromere puffing phenomenon.
The treatment of Roberts syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, surgeons, cardiologists, neurologists, eye specialists, and other health care professionals may need to systematically and comprehensively plan an affected child’s treatment.
Individuals with Roberts Syndrome may benefit from surgery for facial and limb defects. Prosthetic devices can also reduce problems associated with missing limbs.
Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.
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Gordillo M, Vega H, Jabs EW. ESCO2 and Roberts syndrome. In: Epstein CJ, Erickson RP, Wynshaw-Boris A, eds. Inborn Errors of Development. 2 ed, Chap 111. New York: Oxford University Press; 2008:1011-9.
Mandal AK. Roberts Pseudothalidomide Syndrome. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:244-5.
Buyse ML., ed. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific Publications; For: The Center for Birth Defects Information Services Inc; 1990.
Jones KL., ed. Smith’s Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, PA: W. B. Saunders Co: 1997:298.
Gorlin RJ, et al., eds. Syndromes of the Head and Neck, 3rd ed. New York, NY: Oxford University Press; 1990:735-8.
Vega H, Trainer AH, Gordillo M, et al. Phenotypic variability in 49 cases of ESCO2 mutations, including novel missense and codon deletion in the acetyltransferase domain, correlates with ESCO2 expression and establishes the clinical criteria for Roberts syndrome. J Med Genet. 2010;1:30-7.
Schule B, Oviedo A, Johnston K, Pai S, Francke U. Inactivating mutations in ESCO2 cause SC Phocomelia and Roberts syndrome: no phenotype-genotype correlation. Am J Med Genet. 2005;117-28.
Krantz ID, McCallum J, DeScipio C, Kaur M, Gillis LA, Yaeger D, Jukofsky L, Wasserman N, Bottani A, Morris CA, Nowaczyk MJ, Toriello H, Bamshad MJ, Carey JC, Rappaport E, Kawauchi S, Lander AD, Calof AL, Li HH, Devoto M, Jackson LG. Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B. Nat Genet. 2004 Jun;36(6):631-5.
Hwang K, et al. Roberts syndrome, normal cell division, and normal intelligence. J Craniofacial Surg. 2002;13:390-4.
Maheshwari A, et al. Roberts-SC phocomelia syndrome. Indian J Pediatr. 2001;68:557-9.
McDaniel LD, et al. Novel assay for Roberts syndrome assigns variable phenotypes to one complementation group. Am J Med Genet. 2000;93:223-9.
Camlibel T, et al. Roberts SC phocomelia with isolated cleft palate, thrombocytopenia, and eosinophilia. Genet Couns. 1999;10:157-61.
Petrikovsky BM, et al. Prenatal diagnosis of pseudothalidomide syndrome in consecutive pregnancies of a consanguineous couple. Ultrasound Obstet Gynecol. 1997;10:425-8.
Concolino D, et al. A mild form of Roberts/SC phocomelia syndrome with asymmetrical reduction of upper limbs. Clin Genet. 1996;49:274-6.
Van den Berg DJ, Francke U. Roberts syndrome: a review of 100 cases and a new rating system for severity. Am J Med Genet. 1993;15:1104-23.
Van den Berg DJ, Francke U. Sensitivity of Roberts syndrome cells to gamma radiation, mitomycin C, and protein synthesis inhibitors. Somat Cell Mol Genet. 1993;19:377-92.
Holden KR, Jabs EW, Sponseller PD. Roberts/pseudothalidomide syndrome and normal intelligence: approaches to diagnosis and management. Dev Med Child Neurol. 1992;34:534-9.
Sherer DM, et al. Prenatal sonographic features and management of a fetus with Roberts-SC phocomelia syndrome (pseudothalidomide syndrome) and pulmonary hypoplasia. Am J Perinatol. 1991;8:259-62.
Keppen LD, et al. Roberts syndrome with normal cell division. Am J Med Genet. 1991;38:21-4.
Romke C, et al. Roberts syndrome and SC phocomelia. A single genetic entity. Clin Genet. 1987;31:170-7.
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:268300; Last Update: 03/26/2013. Available at http://omim.org/entry/268300 Accessed May 12, 2015.
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:269000; Last Update: 03/26/2013. Available at: http://omim.org/entry/269000 Accessed May 12, 2015.
Gordillo M, Vega H, Jabs EW. Roberts Syndrome. 2006 Apr 18 [Updated 2013 Nov 14]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1153/ Accessed May 12, 2015.
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