This is a rare disorder affecting several parts of the body that are apparent at the birth of the infant. The characteristic feature of this condition is the abnormal growth in the brain known as a hypothalamic hamartoma which usually does not cause any problems but in some case, it can lead to seizures and hormone abnormalities. The symptoms of the condition can vary among the affected cases and rarely they experience serious complications.
Causes
This syndrome develops because of a mutation in the gene identified as GLI3 which produces a protein that controls gene expression. This gene expression regulates a process where the genes are turned on or off in certain cells at the specific times. This is important for the development and the normal shaping of various tissues and organs of the body before the birth. Because of the genetic mutation, the GLI3 protein produced is abnormally short that can only turn off target genes. This condition is inherited in an autosomal dominant pattern meaning a single defective gene in each cell can cause the condition. In some case, it can also develop among people as the result of a new mutation in the gene with no history of the syndrome in the family.
Symptoms
The symptoms associated with this syndrome can vary greatly among the affected cases. Some of the individuals may only experience a few of the features while others can experience the majority of the symptoms associated with the condition. Some of the common features include the presence of an extra digit (polydactyly), a fusion of certain fingers and the improper development of the nails. Additional features can include an obstruction of the anal opening (imperforate anus), seizures and malformation of the hypothalamus (hypothalamic hamartoma) that can cause abnormalities in the function of the pituitary. This can result in symptoms such as an abnormally small penis, growth hormone deficiency and the low functioning of the thyroid (hypothyroidism). The decreased or the absent pituitary function can cause low blood sugar (hypoglycemia), high acid levels in the blood and body tissue. The facial and head abnormalities include small ears that are rotated toward the back of the head, a short nose, a small tongue, an abnormal cleft in the larynx, a presence of certain teeth at birth, abnormally short limbs and improper development of the kidneys or the heart.
Diagnosis
The diagnosis is based on a clinical evaluation, history of the family and with various specialized tests. An MRI can help detect the location and the size of hamartoma and additional tests may include renal ultrasonography and fiberoptic laryngoscopy. The genetic testing can identify the mutation responsible for the development of this condition.
Treatment
Children with the absent pituitary function need to be treated with hormone replacement therapy which can resolve its associated symptoms. A regular examination is required to monitor the malformation of hypothalamic. Surgical intervention may be necessary for the removal of extra digits and in the case of seizures, anticonvulsant medication can help treat the condition.
References
https://rarediseases.org/rare-diseases/pallister-hall-syndrome/
https://rarediseases.info.nih.gov/diseases/7305/pallister-hall-syndrome
https://ghr.nlm.nih.gov/condition/pallister-hall-syndrome#inheritance
