What are the other Names for this Condition? (Also known as/Synonyms)

• Cleft Lip Palate-Tetraphocomelia Syndrome
• Roberts-SC Phocomelia Syndrome
• Pseudothalidomide Syndrome

What is Roberts Syndrome? (Definition/Background Information)

• Roberts Syndrome is a genetic disorder characterized by limb and facial abnormalities. Affected individuals are born with abnormalities of all four limbs and typically have shortened arm and leg bones (hypomelia) 
• They may also havephocomelia(in severe cases), abnormal or missing fingers and toes, joint deformities (contractures), and numerous facial abnormalities includingcleft lip with or without cleft palate,micrognathia, ear abnormalities,hypertelorism, down-slantingpalpebral fissures, small nostrils, and a beaked nose
• Microcephaly,intellectual disability, and heart, kidney or genital abnormalities may also be present
• Roberts Syndrome is caused by mutationsin theESCO2geneand isinheritedin an autosomal recessive pattern 
• Infants with a severe form of Roberts Syndrome are often stillborn or die shortly after birth, while mildly affected individuals may live into adulthood 

(Source: Roberts Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Roberts Syndrome? (Age and Sex Distribution)

• Roberts Syndrome is a rare congenital disorder. The presentation of symptoms may occur at birth
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Roberts Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since Roberts Syndrome can be inherited
• Currently, no other risk factors have been clearly identified for the condition

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Roberts Syndrome? (Etiology)

• Roberts Syndrome is caused by mutationsin theESCO2geneand isinheritedin an autosomal recessive pattern 

(Source: Roberts Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected)

What are the Signs and Symptoms of Roberts Syndrome?

The signs and symptoms of Roberts Syndrome vary, but may include the following:

Very frequently present symptoms in 80-99% of the cases:

• Aplasia/hypoplasia of the thumb
• Bowing of the long bones
• Brachycephaly
• Clinodactyly of the 5th finger
• Complete duplication of thumb phalanx
• Hypertelorism
• Hypoplasia of the radius
• Malar flattening
• Mesomelic arm shortening
• Microcephaly
• Phocomelia
• Postnatal growth retardation
• Proximal placement of thumb
• Radial deviation of finger
• Severe intrauterine growth retardation
• Sparse hair
• Underdeveloped nasal alae

Frequently present symptoms in 30-79% of the cases:

• Abnormality of cardiovascular system morphology
• Absent earlobe
• Brachydactyly
• Cataract
• Cleft upper lip
• Clitoral hypertrophy
• Cryptorchidism
• External ear malformation
• Intellectual disability
• Long penis
• Micrognathia
• Midface capillary hemangioma
• Premature birth
• Proptosis
• Radioulnar synostosis
• Underdeveloped supraorbital ridges

Occasionally present symptoms in 5-29% of the cases:

• Bilateral single transverse palmar creases
• Blue sclerae
• Finger syndactyly
• Glaucoma
• High palate
• Knee flexion contracture
• Microphthalmia
• Nystagmus
• Patellar aplasia
• Polycystic kidney dysplasia
• Polyhydramnios
• Progressive flexion contractures
• Sandal gap
• Short neck
• Synostosis of carpal bones
• Thrombocytopenia
• Wrist flexion contracture

In addition to the above, the following signs and symptoms may also be present:

• Abnormality of the metacarpal bones
• Accessory spleen
• Ankle contracture
• Atrial septal defect
• Bicornuate uterus
• Biliary tract abnormality
• Cafe-au-lait spot
• Cleft eyelid
• Cranial nerve paralysis
• Cystic hygroma
• Downslanted palpebral fissures
• Elbow flexion contracture
• Enlarged labia minora
• Frontal encephalocele
• Hand oligodactyly
• Horseshoe kidney
• Hydrocephalus
• Hypospadias
• Low-set ears
• Narrow naris
• Opacification of the corneal stroma
• Patent ductus arteriosus
• Posteriorly rotated ears
• Premature separation of centromeric heterochromatin
• Shallow orbits
• Syndactyly
• Talipes equinovalgus
• Tetraphocomelia
• Ventricular septal defect
• Wide nasal bridge

(Source: Roberts Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Roberts Syndrome Diagnosed?

The diagnosis of Roberts Syndrome is suspected in individuals with the following:

• Prenatal growth delay ranging from mild to severe. Average birth length and weight is typically below the third percentile in most affected infants
• Limb malformations including bilateral, symmetric tetraphocomelia (phocomeliaof all 4 limbs) or hypomelia (underdevelopment of the limbs) caused by mesomelic shortening (shortening of the middle part of the limb). Upper limbs are typically more severely affected than lower limbs. Other limb malformations includeoligodactylywith thumb aplasia (lack of formation) or hypoplasia (underdevelopment),syndactyly,clinodactyly, and elbow and knee flexioncontractures(inability to fully straighten the arms and legs)
• Craniofacial abnormalitiesincluding bilateralcleft lip and/or palate,micrognathia(small jaw), hypertelorism (widely-spaced eyes), exophthalmos (bulging eyes), downslantingpalpebral fissures, malar hypoplasia (underdeveloped cheek bones), hypoplastic nasal alae, and ear malformations
• The diagnosis of Roberts Syndrome relies on acytogeneticblood test of individuals with the above features. Cytogenetic testing would show the characteristicchromosomal abnormalitiesthat are present in individuals with the condition 
• Molecular genetic testing to check for or confirm ESCO2 gene mutations

(Source: Roberts Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Roberts Syndrome?

The complications of Roberts Syndrome may include:

• Loss of vision
• Low self-esteem
• Inability to live independently owing to intellectual deficit

Complications may occur with or without treatment, and in some cases, due to treatment also

How is Roberts Syndrome Treated?

There is no cure for Roberts Syndrome, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that may develop.

How can Roberts Syndrome be Prevented?

Roberts Syndrome may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Roberts Syndrome? (Outcomes/Resolutions)

• The prognosis of Roberts Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any
• Infants with a severe form of Roberts Syndrome are often stillborn or die shortly after birth, while mildly affected individuals may live into adulthood 

(Source: Roberts Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Additional and Relevant Useful Information for Roberts Syndrome:

Roberts Syndrome is also known by the following names: 

• Appelt-Gerken-Lenz Syndrome 
• Hypomelia Hypotrichosis Facial Hemangioma Syndrome
• Long Bone Deficiencies Associated with Cleft Lip-Palate 
• RBS
• Roberts Syndrome/SC Phocomelia 
• Roberts Tetraphocomelia Syndrome
• SC Phocomelia Syndrome (mild variant of Roberts Syndrome)
• Tetraphocomelia-Cleft Palate Syndrome

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/