Goldenhar Syndrome

Common birth defect of vascular origin involving first and second branchial arch derivatives, resulting mainly in hemifacial microsomia with anomalies of the ear, eye, and vertebral bodies. Usually associated with cardiovascular anomalies including ventriculoseptal defect, atrial septal defect, patent ductus arteriosus, tetralogy of Fallot, and coarctation of the aorta. Arnold-Chiari syndrome and hydrocephalus are reported. Airway problems (unilateral hypoplasia of the facial bones and muscles). Epibulbar dermoids. Limited mouth opening, micrognathia, cleft palate.

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Facio-Auriculo-Vertebral Sequence (or Spectrum) (FAV Sequence); Goldenhar-Gorlin Syndrome; Hemifacial Microsomia; Oculo-Auriculo-Vertebral Dysplasia (OAV Dysplasia); Oculo-Auriculo-Vertebral Anomaly (or Spectrum).

Described by Maurice Goldenhar, an American physician (1924-2002) who attended medical school in Geneva and in 1940 emigrated from Belgium to the United States. He was a general practitioner. The “Maurice Goldenhar Family Medicine Update,” Stony Brook University Hospital, State University of New York, is named in his honor.

Frequency ranges from 1:3000-26,500 live births. Male-to-female ratio is 3:2. Infants born to Gulf War veterans displayed a higher rate of Goldenhar syndrome, probably secondary to toxic exposures.

Most cases are sporadic; familial cases are consistent with autosomal recessive, autosomal dominant, and multifactorial patterns of transmission. Gene location has not been identified.

Vascular disruption in the blood supply to the first and second branchial arches, especially at the time of switching from stapedial to external carotid artery supply, is believed to be the cause in many cases of the Goldenhar anomaly; this disruption could be genetically linked. Another hypothesis suggests that a defect of blastogenesis results from deficiency in migration of neural crest cells, deficiency of mesodermal formation, or defective interaction between neural crest cells and mesoderm. A transgenic mouse line model with autosomal dominant hemifacial microsomia suggested the anomaly consisted of a mutational deletion (23 kb at least) on the locus Hfm (hemifacial microsomia-associated locus) on chromosome 10 (in the mouse). The disorder may be present in monozygotic twins, with only one twin being affected.

Based on the clinical features. Radiographic studies of the vertebral column and the malformations of the mandible and its annexes may be a useful diagnostic aid. Muscular lesions (hypotrophic and hypoplastic muscles) are associated with these skeletal malformations.

Variable phenotypic expression, ranging from mild to severe cases even within the same affected family. The presence of a scleral dermolipoma on the lateral aspect of the eyeball is a condition sine qua non for Goldenhar syndrome. Associated malformations include facial asymmetry (right side in 60% of cases), mandibular hypoplasia, macrostomia, unilateral hypoplastic palate, unilateral hypoplasia of tongue muscles, parotid agenesis, epibulbar dermolipomas, upper eyelid coloboma, blepharophimosis, microphthalmia (even anophthalmia), anomalies of the ear (external and middle ear are frequently involved, inner ear may be involved, hearing loss may be conductive or mixed, preauricular cartilaginous tags or sinuses, external auditory canal atresia), scalp hemangiomas, vertebral dysplasia, and acroosteolysis of terminal phalanges. Other manifestations include microcephaly or hydrocephaly with mental retardation in 5 to 15% of patients, Arnold-Chiari malformation, encephalocele, spina bifida, and cardiac malformations. Cervical subluxation at the level C1 and C2 has been described in some patients. Patients often have feeding difficulties, and they are prone to develop obstructive sleep apnea. Normal lifespan is usual.

Physical examination. Sparing techniques of blood loss (autotransfusion program is recommended if extensive reconstructive surgery is planned). Evaluation for difficult intubation due to mandibular hypoplasia. Standard preoperative laboratory examinations are appropriate in most patients (blood chemistry, blood group, complete blood cell count, coagulation). Echocardiography to exclude associated cardiac defects (atrial and ventricular septal defects, patent ductus arteriosus, tetralogy of Fallot, coarctation of the aorta).

Must be prepared for difficult laryngoscopy and tracheal intubation. Some patients have subluxation of C1-C2. Plastic and/or maxillofacial surgery are often required for correction of malocclusion and cleft palate. Blood loss may be significant and require invasive monitoring of hemodynamic parameters, estimation of blood loss, and repeated blood gas and electrolyte analyses. Postoperative care often requires transfer to an intensive care unit and prolonged mechanical ventilation until the facial swelling (in the case of reconstructive surgery) has decreased to a level safe enough for extubation.

None currently identified that are specific to this condition. Muscle relaxants should be avoided until the airway has been secured. The only pharmacological implications are those associated with the cardiovascular anomalies. Subacute bacterial endocarditis prophylaxis may be necessary.

Aksu Stockhausen Syndrome: This autosomal dominant medical condition is defined by the association of brachial arch defects. Characterized by the presence of anotia/microtia, microstomia, preauricular pits, respiratory distress, pharyngeal abnormality, hearing loss, sacral sinus/dimple, hypertonia, spasticity, and muscle rigidity. A proper evaluation of the airway must be done to eliminate problems related to difficult airway management during face-mask ventilation and tracheal intubation. The potential for hyperkalemia following the administration of succinylcholine must be considered if hypertonia is present.

CHARGE Syndrome: A life-threatening, congenital syndrome with multiple anomalies consisting of choanal atresia, coloboma, heart defects, mental and growth retardation, genital and urinary anomalies, and ear anomalies with deafness. Prognosis worsens if concomitant cyanotic heart lesions, esophageal atresia or central nervous system anomalies are present.

Treacher Collins Syndrome: Autosomal dominant polymalformative syndrome characterized by craniofacial malformations, including hypoplastic zygomatic arches and supraorbital rims, mandibular hypoplasia, micrognathia, macrostomia, palatal malformation, palpebral fissures, and coloboma.

Franceschetti Klein Syndrome: Mandibulofacial dysostosis presenting less severe micrognathia than observed in Pierre Robin syndrome. The facial appearance is characterized by palpebral fissures sloping downward the outer canthi, colobomas (lower eyelids), large mouth but receding chin. Although similar to Treacher Collins syndrome, in this situation the mandible is not as hypoplastic; however, the undersurface is profoundly concave.

Pierre Robin Syndrome: Micrognathia with associated pseudomacroglossia, glossoptosis, and high arched or cleft palate. The posterior displacement of the genioglossus muscle contributes to the abnormal tongue position. Severe micrognathia and small mouth opening.

Trisomy 22: The complete form is usually lethal; mosaicism, however, has a good survival rate. Intrauterine growth retardation, microcephaly, facial malformations (hypertelorism, epicanthal folds, midface hypoplasia, low-set ears), digital malformations, and genitourinary malformations in males; cleft palate, cardiac and anal malformations are common features.