Pallister-Hall Syndrome

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

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

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.

Prevalence estimated to fewer than 1000 patients.

Associated with mutations in the GLI3 gene (short arm chromosome 7), a gene regulating other genes in early fetal development; most cases are sporadic, but cases of autosomal dominant inheritance have been observed.

Unknown.

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.

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 is 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.

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.

Tracheal intubation may be difficult in case of microretrognathia and in the presence of an anomalous epiglottis; anomalies of the larynx or trachea may require an endotracheal tube a size smaller than predicted by age. In the presence of a laryngeal cleft, the maintenance of spontaneous respiration is highly recommended. The anesthetic conduct is dictated by the presence of cardiac anomaly.

Antibioprophylaxis in case of cardiac defect.

Greig Cephalopolysyndactyly Syndrome: Characterized by polydactyly, syndactyly, craniofacial malformations frontal bossing, an abnormally broad nasal bridge, and ocular hypertelorism. It is suggested that the inheritance is an autosomal dominant pattern.

Oral-Facial-Digital Syndrome (OFD): A rare condition categorized into types I to IV. Symptoms common to all four types include neuromuscular disturbances, overgrowth of the frenulum, epicanthus, broad-based nose, polydactyly and syndactyly, extra cranial plate divisions, and clefts of the tongue, jaw, and/or lip. Other clinical features include mental disturbances, dental anomalies, and exotropia.

Holt-Oram Syndrome: Characterized by distinctive malformations of the bones of the thumbs and upper limbs and/or congenital heart defects. The thumbs may be absent or hypoplastic or triphalangic. Hypoplasia of the scaphoid bones, metacarpals, and upper limb (radius, ulna, and humerus) bones. The congenital heart defects include ventricular and atrial septal defect.

McKusick-Kaufman Syndrome: Characterized by hydrometrocolpos. It develops in females and is associated with anomalies of the limbs (postaxial polydactyly) and congenital heart malformation. The same presentation associated with urogenital anomalies (e.g., hypospadias, prominent scrotal raphe) has been reported in male.

Hydrolethalus Syndrome: Characterized by severe central nervous system malformations (brain and spine) and polydactyly of the hands and toes. Two great toes on each foot, hypoplastic eyes, micrognathia, and poorly formed nose are common features. The presence of macrocephaly with frontal and occipital protuberances, postaxial hexadactyly, and duplicated hallux are characteristics. The association with lung and heart abnormalities is reported in more than 50% of cases. They consist of a large aortic valve (AV) communis defect, stenosis of the airway, and abnormal lobation of the lungs.

Smith-Lemli-Opitz Syndrome: A rare inherited disorder of lipid metabolism consisting of a deficiency of the 7-dehydrocholesterol reductase. In type II, the severe form, infants may not survive the newborn period. A less severe clinical expression (type I) may include a small, abnormally long and narrow head, eye abnormalities, a broad nasal tip with anteverted nostrils, broad lateral ridges in the roof of the mouth, and microglossia. Other features include simian creases, syndactyly, unusual fingertip skin patterns, and genital abnormalities. The incidence occurs in relatively high frequency: approximately 1 in 20,000 to 30,000 births in populations of northern and central European background.