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

• Joubert Syndrome with Orofaciodigital Defect
• Oral-Facial-Digital Syndrome Type 6 (OFD6)
• Váradi-Papp Syndrome

What is Polydactyly-Cleft Lip/Palate-Psychomotor Retardation Syndrome? (Definition/Background information)

• Polydactyly-Cleft Lip/Palate-Psychomotor Retardation Syndrome, also known as Joubert Syndrome with Orofaciodigital Defect (or Oral-Facial-Digital Syndrome Type 6, OFD6) is a very rare subtype of Joubert syndrome and related disorders (JSRD), characterized by the neurological features of JS associated with orofacial anomalies and often polydactyly
• Typical oral findings include bifid or lobulated tongue, lingual hamartomas and multiple oral frenulae, but cleft lip and/or palate can also be present
• Polydactyly is typically mesaxial with Y-shaped metacarpals, but can also be preaxial or postaxial. A subset of patients present with hypothalamic hamartoma that has never been reported in other JSRD subgroups

(Source: Orofaciodigital syndrome type 6; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Who gets Polydactyly-Cleft Lip/Palate-Psychomotor Retardation Syndrome? (Age and Sex Distribution)

• Polydactyly-Cleft Lip/Palate-Psychomotor Retardation Syndrome is a rare disorder. The exact prevalence of the disorder is not known
• The onset of symptoms may occur at birth or in infancy
• Both males and females may be affected by this disorder. However, in cases where the condition is transmitted in an X-linked manner, the condition predominantly occurs in males
• Worldwide, individuals of all races and ethnicities may be affected

What are the Risk Factors for Polydactyly-Cleft Lip/Palate-Psychomotor Retardation Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since Polydactyly-Cleft Lip/Palate-Psychomotor Retardation Syndrome can be inherited
• Currently, no other risk factors have been clearly identified for the syndrome

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 Polydactyly-Cleft Lip/Palate-Psychomotor Retardation Syndrome? (Etiology)

• The genetic cause of Polydactyly-Cleft Lip/Palate-Psychomotor Retardation Syndrome is not known the present time
• The condition may be inherited either in an autosomal recessive or X-linked recessive manner

Autosomal recessive inheritance: 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).

X-linked recessive pattern of inheritance: The gene associated with this condition may be located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

What are the Signs and Symptoms of Polydactyly-Cleft Lip/Palate-Psychomotor Retardation Syndrome?

The signs and symptoms of Polydactyly-Cleft Lip/Palate-Psychomotor Retardation Syndrome may include:

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

• Abnormal oral frenulum morphology
• Ataxia
• Bilateral cryptorchidism
• Biparietal narrowing
• Brachydactyly
• Broad nasal tip
• Cleft palate
• Conductive hearing impairment
• Epicanthus
• Esotropia
• Failure to thrive
• Feeding difficulties in infancy 
• Finger clinodactyly
• Frontal bossing
• Gait disturbance
• Generalized hypotonia
• Global developmental delay
• Hamartoma of tongue
• High palate
• Hypertelorism
• Hypoplasia of olfactory tract
• Intellectual disability
• Lobulated tongue
• Long face
• Low-set, posteriorly rotated ears
• Micrognathia
• Molar tooth sign on MRI
• Nystagmus
• Preaxial polydactyly
• Short stature
• Syndactyly
• Tongue nodules

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

• Abnormal heart morphology
• Abnormality of neuronal migration
• Aplasia/Hypoplasia of the corpus callosum
• Apnea
• Central Y-shaped metacarpal
• Cerebellar vermis hypoplasia
• Episodic tachypnea
• Foot polydactyly
• Hand polydactyly
• Highly arched eyebrow
• Hypothalamic hamartoma
• Mesoaxial polydactyly
• Midline notch of upper alveolar ridge
• Prominent nasal bridge
• Renal agenesis            
• Seizures
• Tremor

(Source: Microsomia Hemifacial Radial Defects; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Polydactyly-Cleft Lip/Palate-Psychomotor Retardation Syndrome Diagnosed?

Polydactyly-Cleft Lip/Palate-Psychomotor Retardation Syndrome is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

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 Polydactyly-Cleft Lip/Palate-Psychomotor Retardation Syndrome?

The complications of Polydactyly-Cleft Lip/Palate-Psychomotor Retardation Syndrome may include:

• Difficulties with movement
• Risk of falls and injuries, if seizures are present
• Embarrassment and low self-esteem, due to physical appearance

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

How is Polydactyly-Cleft Lip/Palate-Psychomotor Retardation Syndrome Treated?

There is no cure for Polydactyly-Cleft Lip/Palate-Psychomotor Retardation Syndrome, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops.

How can Polydactyly-Cleft Lip/Palate-Psychomotor Retardation Syndrome be Prevented?

Currently, Polydactyly-Cleft Lip/Palate-Psychomotor Retardation Syndrome may not be preventable, since it is a genetic disorder.

• 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 Polydactyly-Cleft Lip/Palate-Psychomotor Retardation Syndrome? (Outcomes/Resolutions)

• The prognosis of Polydactyly-Cleft Lip/Palate-Psychomotor Retardation Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Polydactyly-Cleft Lip/Palate-Psychomotor Retardation Syndrome:

Polydactyly-Cleft Lip/Palate-Psychomotor Retardation Syndrome may also be known by the following additional synonyms:

• Orofaciodigital Syndrome Type 6
• Polydactyly-Cleft Lip/Palate-Psychomotor Retardation 
• Váradi Syndrome