Pallister-Hall syndrome


Pallister-Hall syndrome is an extremely rare developmental disorder marked by a spectrum of features ranging from mild (extra fingers or toes or a non-cancerous malformation in the hypothalamus region of the brain) to severe (laryngotracheal cleft, an opening between the windpipe and voicebox that can be fatal in newborns).


* Abnormalities of the head, neck, and facial areas including short neck, short midface, flat nasal bridge, small tongue, noticeable underdevelopment of one jaw compared to the other, asymmetric skull, cleft palate and other irregularities of the palate, cleft larynx or epiglottis, cysts on the gums, and ears that are small, low-set, and abnormally rotated toward the back of the head. * Hypothalamic hamartoblastoma, a non-cancerous tumor in the hypothalamus. It grows at the same rate as nearby brain tissue, up to 4 cm across, taking the place of the hypothalamus. Most hypothalamic hamartomas have no symptoms, but in some cases they can cause neurological problems including gelastic epilepsy, which causes chest and diaphragm movements similar to those that occur during laughter. * Inhibited flow of cerebrospinal fluid in the brain. * Limb abnormalities including short limbs, extra fingers or toes (central or postaxial polydactyly), webbing of fingers or toes (syndactyly), abnormally small fingernails or toenails, or absent nails. * Respiratory abnormalities including underdeveloped or abnormally developed lungs * Anus lacking the usual opening * Congenital heart defects * Kidneys with abnormal development or placement * Underdeveloped or abnormally developed adrenal, pituitary, or thyroid glands. This can lead to decreased activity of these glands. Some Pallister-Hall newborns cannot survive due to insufficient activity of the adrenal gland. An underdeveloped pituitary gland can also have lethal consequences. Symptoms of hypopituitarism may include hypoglycemia, jaundice, or unusual drowsiness. * In males, unusually small penis, underdeveloped testicles, or failure of one or both testes to descend normally * Retarded growth in most patients * Mild mental retardation * Spinal abnormalities * Dislocated hips * Signs of puberty may appear unusually early


The most common cause of primary hypopituitarism in adults is a tumor. Other causes include congenital defects (hypoplasia or aplasia of the pituitary gland); pituitary infarction (most often from postpartum hemorrhage); or partial or total hypophysectomy by surgery, irradiation, or chemical agents; and, rarely, granulomatous disease (tuberculosis, for example). Occasionally, hypopituitarism may have no identifiable cause, or it may be related to autoimmune destruction of the gland. Secondary hypopituitarism stems from a deficiency of releasing hormones produced by the hypothalamus — either idiopathic or possibly resulting from infection, trauma, or a tumor. Primary hypopituitarism usually develops in a predictable pattern of hormonal failures. It generally starts with hypogonadism from gonadotropin failure (decreased FSH and LH levels). In adults, it causes cessation of menses in females and impotence in men. Growth hormone (GH) deficiency follows; in children, this causes short stature, delayed growth, and delayed puberty. In adults, it causes osteoporosis, decreased lean-to-fat body mass index, adverse lipid changes, and subtle emotional dysphoria and lethargy. Subsequent failure of thyrotropin (decreased TSH levels) causes hypothyroidism; finally, adrenocorticotropic failure (decreased corticotropin levels) results in adrenal insufficiency. However, when hypopituitarism follows surgical ablation or trauma, the pattern of hormonal events may not necessarily follow this sequence. Sometimes, damage to the hypothalamus or neurohypophysis from one of the above leads to diabetes insipidus.


Both clinical examination and family history are used to diagnose Pallister-Hall syndrome. The hallmark clinical findings are hypothalamic hamartoma (a non-cancerous tumor in the hypothalamus), as well as extra fingers or toes. Another sign useful for diagnostic purposes is bifid epiglottis, a cleft in the thin flap of cartilage behind the base of the tongue. This particular malformation is almost never seen except in cases of Pallister-Hall syndrome. It rarely causes problems. Prenatal testing may be conducted by ultrasound, however its effectiveness in detecting Pallister-Hall syndrome is not conclusive. A molecular genetic test exists to scan the coding regions of the GL13 gene for mutations, but as of early 2001 such testing was available only for scientific research purposes.


Because of the broad range and severity of Pallister-Hall signs and symptoms, the prognosis varies widely from case to case. In families in which multiple cases of Pallister-Hall syndrome exist, the prognosis for any new case is likely to be similar to the existing cases. Mild forms of the syndrome have been identified in a number of large, healthy families believed to have a normal life expectancy. In cases that occur in isolated individuals, the prognosis is based on the specific abnormalities present. Reviews of these abnormalities as reported in scientific literature have limited usefulness because published cases tend to be more severe than those normally encountered. Unless there are life-threatening malformations such as hypopituitarism, the prognosis for these random cases is considered excellent. There is a 50% chance that any child of a Pallister-Hall patient will be affected.


Replacement of hormones secreted by the target glands is the most effective treatment for hypopituitarism. Hormone replacement therapy includes cortisol, T4, and androgen or cyclic estrogen. Prolactin need not be replaced. The patient of reproductive age may benefit from cyclic administration of FSH and human chorionic gonadotropin to induce ovulation. Clinical tip In hypopituitarism, the TSH levels become an unreliable marker for thyroid hormone replacement. Therefore, follow free T4 levels in this patient. Somatrem and others, identical to hGH but the product of recombinant deoxyribonucleic acid technology, have replaced growth hormones derived from human sources. They’re effective for treating dwarfism and stimulating growth increases as great as 6" (15.2 cm) in the first year of treatment. The growth rate tapers off in subsequent years. After pubertal changes have occurred, the effects of somatrem therapy are limited. Occasionally, a child becomes unresponsive to somatrem therapy, even with larger doses, perhaps because antibodies have formed against it. In such refractory patients, small doses of androgen may again stimulate growth, but extreme caution is necessary to prevent premature closure of the epiphyses. Children with hypopituitarism may also need replacement of adrenal and thyroid hormones and, as they approach puberty, sex hormones.