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At a glance

A ciliopathy belonging to the digito-orofacial syndrome group. A congenital X-Linked Syndrome lethal for males. It is characterized by orofacial and digital defects associated with renal failure.

Synonyms

Gorlin-Psaume Syndrome; Papillon-Léage Syndrome; Digito-Orofacial Syndrome I; Orofaciodigital Syndrome I; Gorlin Syndrome I; Papillon-Léage-Psaume Syndrome.

History

Genetic disorder that was first described by Psaume (1962) and known worldwide because of Gorlin’s works. First described in 1954 by E. Papillon-Léage, a French dentist, and J. Psaume, also a French dentist. R. J. Gorlin, an American oral pathologist and geneticist, made this condition internationally known.

Incidence

1:250,000 live births.

Genetic inheritance

X-linked dominant.

Pathophysiology

Caused by mutations in the CXORF5 gene mapped on Xp22.3-p22.2. It is tough that the OFD1 protein regulates the formation, length and organization of the centrosome of primary cilia. It has widespread influence on the organogenesis during fetal development and is clearly essential for fetal survival.

Diagnosis

Clinically evocated in females with characteristic facies, multiple digits anomalies, and renal failure.

Clinical aspects

Features involve head and neck (microcephaly or macrocephaly, micrognathia, frontal bossing, zygomatic hypoplasia, increased cranial base angle, hypertelorism, telecanthus, choroid coloboma, hypoplastic alar cartilage, broad nasal root, short upper lip, median cleft lip, cleft palate, palatal grooves, alveolar notching, hyperplastic oral frenula, lobulated/bifid tongue, tongue hamartomas, missing incisor teeth, supernumerary teeth, periodontal diseases, malocclusion), digits (brachydactyly, clinodactyly, syndactyly), skin (dry scalp, sparse hair, alopecia), central nervous system (hydrocephaly, hydranencephaly, porencephaly, partial agenesis of the corpus callosum, hamartoma of the hypothalamus, gray matter heterotopias, conductive deafness), and kidneys (renal failure, polycystic kidneys). Mild mental retardation and irritability occur in 50% of cases. Seizures, precocious puberty, and short stature can be associated.

Precautions before anesthesia

Evaluate tracheal intubation (clinical, radiographs), neurological function (clinical, CT/MRI scans, EEG), and renal function (clinical, echography, laboratory).

Anesthetic considerations

Tracheal intubation can be difficult and may require adapted anesthetic management. Exclude increased intracranial pressure before neuraxial techniques.

Pharmacological implications

Consider interaction between antiepileptic treatment and anesthetic drugs. Intraoperative fluid regimen and anesthetic drugs choice should consider renal function.

Other conditions to be considered

  • Joubert Syndrome: Rare autosomal recessive disorder associated with hypoplasia or agenesis of the cerebellar vermis resulting in severe ataxia and breathing disorders. Subtype N also characterized by renal pathology (nephronophthisis and polycystic kidney disease).

  • Oculodentodigital Syndrome: Very rare form of bone dysplasia characterized by microphthalmia, microsomia, large jaw, and hypoplasia of the dental enamel. Other possible features are syndactyly or clinodactyly ...

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