Traits

Traits linked to SIX3

SIX homeobox 3

The Human Phenotype Ontology links 137 traits to SIX3, by body system: features seen in people with one of the gene's rare conditions.

SIX3

Abnormality of the nervous system

Trait	How often it is seen
Global developmental delay	Always
Abnormal central motor function	Often (30–79%)
Abnormal corpus callosum morphology	Often (30–79%)
Abnormal morphology of the olfactory bulb	Often (30–79%)
Abnormal shape of brainstem	Often (30–79%)
Abnormal shape of midbrain	Often (30–79%)
Abnormality of the autonomic nervous system	Often (30–79%)
Absent speech development	Often (30–79%)
Alobar holoprosencephaly	Often (30–79%)
Anxiety	Often (30–79%)
Aplasia of the falx cerebri	Often (30–79%)
Attention deficit	Often (30–79%)
Behavioral abnormality	Often (30–79%)
Communication delay	Often (30–79%)
Depression	Often (30–79%)
Epilepsy	Often (30–79%)
Impulsivity	Often (30–79%)
Inability to walk	Often (30–79%)
Intellectual disability	Often (30–79%)
Irritability	Often (30–79%)
Lack of feeling, emotion, interest	Often (30–79%)
Lethargy	Often (30–79%)
Limb dystonia	Often (30–79%)
Neural tube defect	Often (30–79%)
Oromotor apraxia	Often (30–79%)
Poor speech	Often (30–79%)
Short attention span	Often (30–79%)
Sleep-wake cycle disturbance	Often (30–79%)
Specific learning disability	Often (30–79%)
Abnormal septum pellucidum morphology	Sometimes (5–29%)
Agenesis of corpus callosum	Sometimes (5–29%)
Enlarged brain	Sometimes (5–29%)
Holoprosencephaly	Sometimes (5–29%)
Hypoplasia of the pons	Sometimes (5–29%)
Perisylvian polymicrogyria	Sometimes (5–29%)
Rhombencephalosynapsis	Sometimes (5–29%)
Semilobar holoprosencephaly	Sometimes (5–29%)
Too much cerebrospinal fluid in the brain	Sometimes (5–29%)
Decrease in size of the outer layer of the brain due to loss of brain cells	Not recorded
Schizencephaly	Not recorded
Small cerebellum	Not recorded

Abnormality of head or neck

Trait	How often it is seen
Blockage of the rear opening of the nasal cavity	Very often (80–99%)
Midnasal stenosis	Very often (80–99%)
Only one upper front tooth	Very often (80–99%)
Abnormally small head	Often (30–79%)
Bifid uvula	Often (30–79%)
Both sided cleft lip	Often (30–79%)
Central cleft upper lip	Often (30–79%)
Cleft palate	Often (30–79%)
Flat nose	Often (30–79%)
High palate	Often (30–79%)
Narrow nasal bridge	Often (30–79%)
Right and left cleft palate	Often (30–79%)
Short philtrum	Often (30–79%)
Tented mouth	Often (30–79%)
Absence of the intermaxillary bone	Sometimes (5–29%)
Absence of the nasal bone	Sometimes (5–29%)
Big calvaria	Sometimes (5–29%)
Cleft of the mouth	Sometimes (5–29%)
Frontoethmoidal encephalocele	Sometimes (5–29%)
Midface retrusion	Sometimes (5–29%)
Mono nostril	Sometimes (5–29%)
Nasal tip, upturned	Sometimes (5–29%)
Proboscis	Sometimes (5–29%)
Short nose	Sometimes (5–29%)
Absent nasal septal cartilage	Not recorded
Central cleft palate	Not recorded
Submucous cleft hard palate	Not recorded
Zygomatic flattening	Not recorded

Abnormality of the endocrine system

Trait	How often it is seen
Abnormal hypothalamus physiology	Often (30–79%)
Abnormality of the endocrine system	Often (30–79%)
Anterior hypopituitarism	Often (30–79%)
Central diabetes insipidus	Often (30–79%)
Diabetes insipidus	Often (30–79%)
Early onset of puberty	Often (30–79%)
Central hypothyroidism	Sometimes (5–29%)
Decreased response to growth hormone stimulation test	Sometimes (5–29%)
Panhypopituitarism	Sometimes (5–29%)
Underactive thyroid	Sometimes (5–29%)
Absent pituitary gland	Not recorded
Small adrenal glands	Not recorded

Abnormality of the musculoskeletal system

Trait	How often it is seen
Abnormal vertebral morphology	Often (30–79%)
Abnormality of the ribs	Often (30–79%)
Decreased muscle tone in infant	Often (30–79%)
Generalized decreased muscle tone	Often (30–79%)
Involuntary muscle stiffness, contraction, or spasm	Often (30–79%)
Abnormality of the skeletal system	Sometimes (5–29%)
EMG: myopathic abnormalities	Sometimes (5–29%)
Flexed joint that cannot be straightened	Sometimes (5–29%)
Low muscle tone in trunk	Sometimes (5–29%)
Scoliosis	Sometimes (5–29%)
Low muscle tone	Not recorded

Abnormality of the digestive system

Trait	How often it is seen
Feeding difficulties	Very often (80–99%)
Poor suck	Very often (80–99%)
Acid reflux	Often (30–79%)
Constipation	Often (30–79%)
Poor swallowing	Often (30–79%)
Vomiting	Often (30–79%)
Abnormal shape of the digestive system	Sometimes (5–29%)
Absence or narrowing of first part of small bowel	Sometimes (5–29%)
Anteriorly placed anus	Sometimes (5–29%)
Gastrostomy tube feeding in infancy	Sometimes (5–29%)

Abnormality of the eye

Trait	How often it is seen
Abnormally close eyes	Always
Abnormality of the eye	Very often (80–99%)
Bulging eye	Often (30–79%)
Cerebral visual impairment	Often (30–79%)
Abnormally small eyeball	Sometimes (5–29%)
Birth defect that causes a hole in the innermost layer at the back of the eye	Sometimes (5–29%)
Cat eye	Sometimes (5–29%)
Cross-eyed	Sometimes (5–29%)
Cyclops eye	Sometimes (5–29%)
Remnants of the hyaloid vascular system	Sometimes (5–29%)

Abnormality of the cardiovascular system

Trait	How often it is seen
Abnormal cardiovascular system morphology	Sometimes (5–29%)
Abnormal heart rate variability	Sometimes (5–29%)
Abnormality of the heart	Sometimes (5–29%)
Narrowing of aorta	Sometimes (5–29%)
Strawberry mark	Sometimes (5–29%)
Tetralogy of Fallot	Sometimes (5–29%)
Single ventricle	Not recorded

Abnormality of the genitourinary system

Trait	How often it is seen
Abnormality of the genitourinary system	Sometimes (5–29%)
Absent kidney	Sometimes (5–29%)
Ambiguous external genitalia	Sometimes (5–29%)
Underdeveloped penis	Sometimes (5–29%)

Growth abnormality

Trait	How often it is seen
Faltering weight	Very often (80–99%)
Growth delay	Very often (80–99%)
Short stature	Very often (80–99%)
Prenatal growth deficiency	Often (30–79%)

Abnormality of the respiratory system

Trait	How often it is seen
Abnormal pattern of respiration	Often (30–79%)
Central apnea	Often (30–79%)
Chronic lung disease	Often (30–79%)

Abnormality of limbs

Trait	How often it is seen
Abnormality of limbs	Sometimes (5–29%)
Hip dislocation	Sometimes (5–29%)

Abnormality of the immune system

Trait	How often it is seen
Aspiration pneumonia	Often (30–79%)
Asthma	Sometimes (5–29%)

Abnormality of prenatal development or birth

Trait	How often it is seen
Premature birth	Often (30–79%)

Abnormality of the ear

Trait	How often it is seen
Sensorineural hearing impairment	Often (30–79%)

Laboratory abnormality

Trait	How often it is seen
Temperature instability	Often (30–79%)

How often is among people with one of the gene's conditions, the most often across them, as the Human Phenotype Ontology records it. These pages describe traits and the research behind them; they are not a diagnosis, and a doctor or genetic counsellor is the person to ask about symptoms.

Where this comes from

The Human Phenotype Ontology, release 2026-09-01: the traits linked to SIX3 and how often each is seen. Find out more at hpo.jax.org.

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