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At a glance

Congenital syndrome characterized by hypothalamic hamartoblastoma with panhypopituitarism and polydactyly. Other features include craniofacial abnormalities, endocrine, cardiac, and renal defects. Laryngeal cleft and epiglottis dysplasia are common. Mild retardation is most often present.

Synonyms

CAVE Complex; Cerebro-Acro-Visceral Early Lethality Complex; Hall-Pallister Syndrome; Congenital Hypothalamic Hamartoblastoma, Hypopituitarism, Imperforate Anus, Postaxial Polydactyly Syndrome.

History

This medical condition was described in 1980 by Judith G. Hall, an American geneticist, after observing these anomalies in six children. Philip D. Pallister, an American pediatrician and human geneticist, contributed to the genetic determination before his retirement in 1981.

Incidence

Prevalence estimated to fewer than 1000 patients.

Genetic inheritance

Autosomal dominant.

Pathophysiology

Associated with mutations in the GLI3 gene on 7p14.1, a gene that produces a transcriptional repressor.

Diagnosis

Hormonal deficiencies; hypothalamic hamartoblastoma on MRI: it extends from the optic chiasma to the interpeduncular fossa, thus replacing the hypothalamus and nuclei originating from the embryogenic hypothalamic plate. Other associated cerebral anomalies may be present, including occipital encephalocele and Dandy-Walker malformation.

Clinical aspects

At birth: variable syndactyly and postaxial polydactyly with imperforate anus or variable degrees of rectal atresia; flat midface and nasal bridge; short nose with anteverted nares; external ears anomalies (absent auditory canals, malformed pinnae); micrognathia. Laryngeal cleft and dysplastic epiglottis are common. Bifid epiglottis is present in more than 40% of patients. Congenital heart disease: atrial septal defect, ventricular septal defect, patent ductus arteriosus, coarctation of aorta. Patients present with kidney dysplasia, testicular hypoplasia, micropenis, and cryptorchidism. Severely affected infants have impaired pituitary function: growth hormone deficiency and hypothyroidism are common; hypocortisolemia and diabetes insipidus are rarer. Hypoplastic adrenal glands. Some cases with precocious puberty. Bifid, hypoplastic, or absent epiglottis at laryngoscopy. Cases of laryngeal cleft have been described. Abnormal tracheal cartilage and anomalies of pulmonary lobation and lung hypoplasia or dysplasia are frequent. The majority of patients described have died by 3 years of age, the major cause of neonatal death being hypoadrenalism. Long-term survivors are on hormonal therapy from birth or early infancy. Headaches are common. Some patients have seizures. Intelligence is usually normal.

Precautions before anesthesia

Check hormonal treatment: it should be continued up to the day of surgery and adapted with the help of the child’s endocrinologist; echocardiography to exclude the presence of a congenital heart defect. A proper evaluation of the airway must be done to eliminate the presence of a laryngeal cleft. The medical history for seizure and antiepileptic medication must be reviewed.

Anesthetic considerations

Tracheal intubation may be difficult in case of microretrognathia and in the presence of an anomalous epiglottis; anomalies of the larynx ...

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