Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen.

Syndrome with characteristics of polysyndactyly, hexadactyly (duplication of the first toe) and complex cardiac malformation (including atrial and ventricular septal defect, single ventricle, aortic dextroposition, or dilation of the right heart). It has been described in six patients from three unrelated families. Other manifestations were present in some patients (i.e. facial dysmorphism, hepatic cysts).

Baraitser-Winter cerebrofrontofacial (BWCFF) syndrome is a multiple congenital anomaly syndrome characterized by typical craniofacial features and intellectual disability. Many (but not all) affected individuals have pachygyria that is predominantly frontal, wasting of the shoulder girdle muscles, and sensory impairment due to iris or retinal coloboma and/or sensorineural deafness. Intellectual disability, which is common but variable, is related to the severity of the brain malformations. Seizures, congenital heart defects, renal malformations, and gastrointestinal dysfunction are also common.

Any hydrolethalus syndrome in which the cause of the disease is a mutation in the HYLS1 gene.

Features the presence of a usually opposable triphalangeal thumb with or without additional duplication of one or more skeletal components of the thumb. The thumb appearance can differ widely in shape (wedge to rectangular) or it can be deviated in the radio-ulnar plane. Also associated with systemic syndromes including Holt-Oram syndrome.

Rubinstein-Taybi syndrome (RSTS) is characterized by distinctive facial features, broad and often angulated thumbs and halluces, short stature, and moderate-to-severe intellectual disability. The characteristic craniofacial features are downslanted palpebral fissures, low-hanging columella, high palate, grimacing smile, and talon cusps. Prenatal growth is often normal, then height, weight, and head circumference percentiles rapidly drop in the first few months of life. Short stature is typical in adulthood. Obesity may develop in childhood or adolescence. Average IQ ranges between 35 and 50; however, developmental outcome varies considerably. Some individuals with EP300-RSTS have normal intellect. Additional features include ocular abnormalities, hearing loss, respiratory difficulties, congenital heart defects, renal abnormalities, cryptorchidism, feeding problems, recurrent infections, and severe constipation.