Opitz-Frias Syndrome

At a glance

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.

Synonyms

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; Oberklaid-Danks Syndrome.

Incidence

Rare, estimated to be 1:50,000 to 1:100,000 live births. However, a number of affected families have been reported.

Genetic inheritance

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.

Pathophysiology

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

Diagnosis

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

Clinical aspects

Originally described as distinct syndromes, the Opitz G and Opitz 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.

Precautions before anesthesia

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.

Anesthetic considerations

Expect difficult tracheal intubation from facial and laryngotracheal malformations. ...