Orofaciodigital syndrome 6

Other Names: Joubert syndrome with orofaciodigital defect; OFD6; Oral-facial-digital syndrome type 6; Polydactyly - cleft lip/palate - psychomotor retardation; Váradi syndrome; Váradi-Papp syndrome; Polydactyly-cleft lip/palate-psychomotor retardation syndrome; Orofaciodigital syndrome type 6; Polydactyly cleft lip palate psychomotor retardation

Orofaciodigital syndrome type-VI (OFDS-VI) is a very rare autosomal recessive disorder distinguished from other types of OFDS by cerebellar dysgenesis and manual central polydactyly with y-shaped central metacarpals.

Epidemiology

The syndrome was first reported by Varadi, et al. in six children in an endogamic gypsy colony of Hungary.

Cause

Two OFD6 patients, including one fetus, were found to carry a homozygous mutation in the TMEM216 gene (11q13.1), but mutations in this gene were excluded in several other patients, and the genetic basis of this condition still remains elusive.

Inheritance

File:Autorecessive.svg

Autosomal recessive inheritance, a 25% chance

Males and females are equally affected and an autosomal recessive pattern of inheritance was observed in familial cases.

Signs and symptoms

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.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 30%-79% of people have these symptoms

• Abnormal oral frenulum morphology
• Ataxia
• Bilateral cryptorchidism
• Biparietal narrowing
• Brachydactyly(Short fingers or toes)
• Broad nasal tip(Broad tip of nose)
• Cleft palate(Cleft roof of mouth)
• Conductive hearing impairment(Conductive deafness)
• Epicanthus(Eye folds)
• Esotropia(Inward turning cross eyed)
• Failure to thrive(Faltering weight)
• Feeding difficulties in infancy
• Finger clinodactyly
• Frontal bossing
• Gait disturbance(Abnormal gait)
• Generalized hypotonia(Decreased muscle tone)
• Global developmental delay
• Hamartoma of tongue
• High palate(Elevated palate)
• Hypertelorism(Wide-set eyes)
• Hypoplasia of olfactory tract
• Intellectual disability(Mental deficiency)
• Lobulated tongue(Bumpy tongue)
• Long face(Elongation of face)
• Low-set, posteriorly rotated ears
• Micrognathia(Little lower jaw)
• Molar tooth sign on MRI
• Nystagmus(Involuntary, rapid, rhythmic eye movements)
• Preaxial polydactyly
• Short stature(Decreased body height)
• Syndactyly(Webbed fingers or toes)
• Tongue nodules

5%-29% of people have these symptoms

• Abnormal heart morphology(Abnormality of the heart)
• Abnormality of neuronal migration
• Aplasia/Hypoplasia of the corpus callosum
• Apnea
• Central Y-shaped metacarpal(Y-shaped central long bones of hand)
• Cerebellar vermis hypoplasia
• Episodic tachypnea
• Foot polydactyly(Duplication of bones of the toes)
• Hand polydactyly(Extra finger)
• Highly arched eyebrow(Arched eyebrows)
• Hypothalamic hamartoma
• Mesoaxial polydactyly
• Midline notch of upper alveolar ridge
• Prominent nasal bridge(Elevated nasal bridge)
• Renal agenesis(Absent kidney)
• Seizure
• Tremor

Diagnosis

Evidence of central polydactyly of the hands and cerebellar anomalies in the presence of minimal orofacial manifestation establishes the diagnosis of the disorder.

Treatment

Management includes genetic counseling and possible medicosurgical supportive interventions.

NIH genetic and rare disease info

• NIH info on Orofaciodigital syndrome 6

Orofaciodigital syndrome 6 is a rare disease.