Pallister-Hall syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Pallister-Hall syndrome is a disorder that affects the development of many parts of the body. Most people with this condition have extra fingers and/or toes (polydactyly), and the skin between some fingers or toes may be fused (cutaneous syndactyly). An abnormal growth in the brain called a hypothalamic hamartoma is characteristic of this disorder. In many cases, these growths do not cause any health problems; however, some hypothalamic hamartomas lead to seizures or hormone abnormalities that can be life-threatening in infancy. Other features of Pallister-Hall syndrome include a malformation of the airway called a bifid epiglottis, an obstruction of the anal opening (imperforate anus), and kidney abnormalities. Although the signs and symptoms of this disorder vary from mild to severe, only a small percentage of affected people have serious complications.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Mutations in the GLI3 gene cause Pallister-Hall syndrome. This gene provides instructions for making a protein that controls gene expression, which is a process that regulates whether genes are turned on or off in particular cells. By interacting with certain genes at specific times during development, the GLI3 protein plays a role in the normal shaping (patterning) of many organs and tissues before birth.

Mutations that cause Pallister-Hall syndrome typically lead to the production of an abnormally short version of the GLI3 protein. Unlike the normal GLI3 protein, which can turn target genes on or off, the short protein can only turn off (repress) target genes. Researchers are working to determine how this change in the protein's function affects early development. It is uncertain how GLI3 mutations can cause polydactyly, hypothalamic hamartoma, and the other features of Pallister-Hall syndrome.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits a mutation in the GLI3 gene from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

This condition is very rare; its prevalence is unknown.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Hypothalamic hamartoma · Obligate (100%)

The presence of a hamartoma of the hypothalamus.

3-4 finger cutaneous syndactyly · Frequent (79-30%)

A soft tissue continuity in the A/P axis between fingers 3 and 4.

Abnormal basal ganglia MRI signal intensity · Frequent (79-30%)

A deviation from normal signal on magnetic resonance imaging (MRI) of the basal ganglia.

Accessory oral frenulum · Frequent (79-30%)

Extra fold of tissue extending from the alveolar ridge to the inner surface of the upper or lower lip.

Adrenocorticotropic hormone deficiency · Frequent (79-30%)

A reduced ability to secrete adrenocorticotropic hormone (ACTH), a hormone that stimulates the adrenal cortex to secrete of glucocorticoids such as cortisol.

Anal atresia · Frequent (79-30%)

Congenital absence of the anus, i.e., the opening at the bottom end of the intestinal tract.

Anteverted nares · Frequent (79-30%)

Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).

Atresia of the external auditory canal · Frequent (79-30%)

Absence or failure to form of the external auditory canal.

Bifid uvula · Frequent (79-30%)

Uvula separated into two parts most easily seen at the tip.

Brachydactyly · Frequent (79-30%)

Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.

Broad thumb · Frequent (79-30%)

Increased thumb width without increased dorso-ventral dimension.

Central adrenal insufficiency · Frequent (79-30%)

A form of adrenal insufficiency related to a lack of ACTH, which leads to a decrease in the production of cortisol by the adrenal glands. Aldosterone production is not usually affected.

Depressed nasal ridge · Frequent (79-30%)

Lack of prominence of the nose resulting from a posteriorly-placed nasal ridge.

Downslanted palpebral fissures · Frequent (79-30%)

The palpebral fissure inclination is more than two standard deviations below the mean.

Other findings in the same source

From: Orphanet

Additional reported features include Gonadotropin deficiency (Frequent (79-30%)); Hemivertebrae (Frequent (79-30%)); Hip dislocation (Frequent (79-30%)); Hypertelorism (Frequent (79-30%)); Intrauterine growth retardation (Frequent (79-30%)); Laryngeal cleft (Frequent (79-30%)); Macrocephaly (Frequent (79-30%)); Mesoaxial polydactyly (Frequent (79-30%)); Microphthalmia (Frequent (79-30%)); Microtia (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Pallister-Hall syndrome is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Pallister-Hall syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.