Goldenhar syndrome results from disrupted development of two specific structures in the embryo, called the first and second branchial arches, during the first few weeks of pregnancy. The exact trigger for this disruption varies and, in most cases, remains unknown. Affecting roughly 1 in 3,000 to 5,000 births, the condition is considered multifactorial, meaning a combination of genetic susceptibility, vascular events in the embryo, and environmental exposures likely work together to cause it.
What Goes Wrong During Early Development
The branchial arches are ridges of tissue that form in the embryo around the fourth week of pregnancy. They serve as the blueprint for most of the face, jaw, and ear structures. The first arch gives rise to the upper and lower jaw bones, the chewing muscles, parts of the ear canal, and two of the three tiny bones inside the middle ear. The second arch produces the third middle ear bone (the stapes), the muscles of facial expression, portions of the hyoid bone in the throat, and additional ear structures.
In Goldenhar syndrome, something interferes with the cells that are building these arches. Two types of disruption have been identified. One involves the failure of certain embryonic cells, including neural crest cells, to migrate properly to where they’re needed. The other involves problems with the blood supply feeding the branchial arches during their rapid growth phase. Either scenario, or a combination of both, can leave these structures underdeveloped on one or both sides of the face. By the time the facial structures finish fusing around the 12th week of pregnancy, the window for normal development has passed.
The Stapedial Artery Theory
One of the most widely accepted explanations centers on a tiny, temporary blood vessel called the stapedial artery. During embryonic weeks three through five, the blood supply to the first branchial arch passes through a relay of three vessels in sequence: first the initial aortic arch, then the stapedial artery (which comes from the second branchial arch), and finally the permanent blood supply from the external carotid artery. This handoff needs to be precisely timed. If anything disrupts the sequence, the rapidly growing tissue of the first and second arches can be starved of blood during a critical growth window.
Researchers confirmed this theory by exposing mice and monkeys to known teratogens (thalidomide and triazene), which produced offspring with facial features closely resembling Goldenhar syndrome. When they examined the embryos under a microscope, the earliest visible problem was bleeding (hematomas) around the developing stapedial artery. Genetically engineered mice designed to mimic the condition showed the same pattern: rupture of the stapedial blood vessels was the first thing to go wrong, followed by tissue damage from reduced blood flow. This vascular disruption theory helps explain why the syndrome so often affects just one side of the face, since a localized bleed would damage only nearby structures.
Genetic Factors
Most cases of Goldenhar syndrome appear sporadically, meaning they occur in families with no prior history of the condition. However, autosomal dominant inheritance has been documented in some families, where a parent with mild features can pass it to a child who may be more noticeably affected.
The gene most clearly linked to the condition so far is MYT1. Research on a group of 73 Brazilian patients found a new variant of this gene predicted to be harmful in five unrelated individuals. Structural changes near the MYT1 gene were also more common in patients than in healthy controls. But the genetics are far from simple. Multiple types of genetic changes and different inheritance patterns appear to be involved, which is part of why no single genetic test can confirm or rule out the syndrome.
Chromosomal abnormalities have also been found in some patients. Deletions in a region of chromosome 22 (22q11.2), better known for causing DiGeorge syndrome, have occasionally appeared in children who have the Goldenhar pattern of facial features. This overlap suggests that certain chromosomal regions may influence branchial arch development in ways that can produce similar-looking conditions through different genetic mechanisms.
Environmental and Maternal Risk Factors
Several prenatal exposures have been linked to a higher risk. Maternal diabetes stands out as one of the strongest: mothers with any form of diabetes, whether pre-existing or developing during pregnancy, had roughly four times the risk of having a child with craniofacial microsomia (the broader category that includes Goldenhar syndrome). Higher parity, meaning having had more previous pregnancies, was associated with about double the risk.
Prenatal exposure to certain medications also raises concern. Retinoids (vitamin A derivatives used in some acne and skin treatments), thalidomide, and the immune-suppressing drug mycophenolate mofetil have all been associated with higher rates of ear and facial underdevelopment. Vasoactive medications taken in the first trimester, particularly in combination with cigarette smoking, have shown an association as well. Interestingly, the relationship between vitamin A and risk appears to go in both directions: while synthetic retinoid drugs increase risk, dietary vitamin A intake (from food sources or prenatal vitamins) was associated with a 70% lower risk, likely reflecting the difference between normal physiological levels and the high doses delivered by pharmaceutical retinoids.
Maternal acute illness during early pregnancy, advanced maternal age, and low birthweight have all appeared as additional risk factors in population studies, though the strength of these associations varies.
Why Most Cases Have No Clear Cause
For the majority of families, no single explanation accounts for why the syndrome occurred. This is consistent with a multifactorial model, where a child may carry a mild genetic susceptibility that only leads to the condition when combined with an environmental trigger or a chance vascular event during a narrow developmental window. The branchial arches develop and fuse over just a few weeks, and the blood supply relay through the stapedial artery is inherently fragile. A small disruption at the wrong moment can have outsized consequences.
This also means that recurrence risk for future pregnancies is generally low in sporadic cases, though it rises in families where a genetic component has been identified. Genetic counseling can help clarify individual risk based on family history and, in some cases, testing for known variants like those in MYT1 or chromosomal regions like 22q11.2.