Opitz-Frias Syndrome

Genetic disorder characterized by craniofacial anomalies, ocular hypertelorism, cleft lip and palate, epicanthal folds, and a wide, flat nasal bridge. Affected males present cryptorchidism, bifid scrotum, and/or hypospadias. The most significant anomalies are the presence of cleft in the larynx and trachea, pulmonary hypoplasia, dysphagia, and respiratory obstruction. Hypoplasia or agenesis of the corpus callosum, kidney abnormalities, cardiac defects, and mental retardation have been reported.

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G Syndrome; X-Linked Opitz G/BBB Syndrome; X-Linked Opitz Syndrome; Opitz-G Syndrome Type I; Opitz BBBG Syndrome Type I; Hypertelorism-Hypospadias Syndrome; Telecanthus-Hypospadias Syndrome.

Rare; however, a number of families have been reported.

X-linked recessive type is based on various defects in the midline 1 (MID1) gene located on Xp22.3, and an autosomal dominant form with variable penetrance has been mapped to chromosome 22q11.2.

MID1 encodes for a protein named midin, which is believed to play a role in anchoring the cellular microtubules that form the cytoskeleton.

Based on clinical features, family history, and genetic testing.

Originally described as distinct syndromes, the G and BBB syndromes are now summarized as a single disorder characterized by hypertelorism, hypospadias. and other midline defects. In particular, congenital heart defects are frequent and include patent ductus arteriosus, atrial septal defect, ventricular septal defect, coarctation of the aorta, and complex malformations, such as tetralogy of Fallot and double-outlet right ventricle (conotruncal anomalies). A variety of genitourinary defects other than hypospadias, such as cryptorchidism, bifid scrotum, and imperforate anus, also belong to the phenotypic spectrum of Opitz syndrome. Other facial anomalies include cleft lip and palate, a broad, flat nasal bridge, micrognathia, and up-slanting or down-slanting palpebral fissures with epicanthal folds. Frequent anomalies are laryngeal malformation (or cleft) and a high carina or tracheoesophageal fistula. Dysphagia associated with recurrent aspiration is common. Achalasia of the esophagus and/or hiatus hernia. MRI may show absent or hypoplastic corpus callosum, or cortical atrophy with ventriculomegaly. Mild-to-moderate mental deficiency with hypotonia.

Careful airway evaluation must be performed. If time allows, consultation with an otorhinolaryngologist must be considered to stage the laryngeal cleft. History of aspiration or the presence of cough during swallowing must be explored during questioning. Dysphagia is a frequent symptom, and recurrent aspirations are not uncommon. Therefore, a chest radiograph should be routine prior to general anesthesia in individuals at risk. Cardiac examination, including echocardiogram, must be performed.

Expect difficult tracheal intubation from facial and laryngotracheal malformations. Maintain spontaneous ventilation until the airway has been secured and gas exchange confirmed. Patients are at risk for aspiration during induction and recovery. May require an endotracheal tube smaller than foreseen by age-based formulas. Recurrent aspiration or lung hypoplasia may limit pulmonary reserve. The further anesthetic approach is determined mainly by the underlying cardiac defect.

Depending on the cardiac function, agents with a potential for myocardial depression should be used with caution.

DiGeorge Syndrome: Genetic defect leading to a wide range of phenotypic presentations, mainly developmental defects in the outflow tract of the heart, hypoparathyroidism with hypocalcemia, and thymic hypoplasia/aplasia with immune defects.

Velocardiofacial Syndrome: Syndrome includes typical facies and cardiac anomalies. Many other malformations can be associated (endocrine and ophthalmic). Anesthetic implications are frequent (intubation, cardiac, infectious). Some patients with Opitz syndrome were found to have deletions on 22q11.2, which are the underlying genetic defects in DG/VCF. However, several findings are distinctive enough to separate Opitz syndrome from DG/VCF.

Eastman-Bixler Syndrome: Characterized by a classic facies (malar hypoplasia, prominent antegonial notch of the mandible), horseshoe kidney, congenital heart defects, muscular hypoplasia, mental retardation, and delayed physical development.