Pallister-Hall Syndrome
Pallister-Hall Syndrome
Overview
Pallister-Hall syndrome (PHS) is a rare genetic disorder characterized by multiple congenital anomalies, including hypothalamic hamartoma, polydactyly, and various visceral malformations. First described by Judith Hall and Philip Pallister in 1980.
Pathophysiology
- Caused by mutations in GLI3 gene
- Affects early embryonic development
- Disrupts sonic hedgehog signaling pathway
- Impacts multiple organ systems
- Variable expressivity
Epidemiology
- Extremely rare disorder
- No gender or ethnic predilection
- Autosomal dominant inheritance
- Many cases represent new mutations
Clinical Manifestations
Central Nervous System
- Hypothalamic hamartoma
- Seizures
- Gelastic epilepsy
- Central precocious puberty
- Neurological symptoms
Limb Abnormalities
- Central polydactyly
- Postaxial polydactyly
- Short fingers (brachydactyly)
- Nail dysplasia
- Digital bifurcation
Craniofacial Features
- Mid-face hypoplasia
- Short nose with flat bridge
- Cleft palate
- Micrognathia
- Dental anomalies
Visceral Anomalies
- Imperforate anus
- Laryngotracheal cleft
- Renal abnormalities
- Congenital heart defects
- Genitourinary malformations
Endocrine Manifestations
- Panhypopituitarism
- Growth hormone deficiency
- Adrenal insufficiency
- Thyroid dysfunction
Diagnostic Approach
Clinical Assessment
- Detailed physical examination
- Family history
- Developmental assessment
- Growth monitoring
Imaging Studies
- Brain MRI (hypothalamic hamartoma)
- Skeletal radiographs
- Renal ultrasound
- Echocardiogram
- Pelvic ultrasound
Laboratory Studies
- Endocrine function tests
- Growth hormone levels
- Thyroid function tests
- Cortisol levels
- Genetic testing (GLI3)
Differential Diagnosis
- Smith-Lemli-Opitz syndrome
- McKusick-Kaufman syndrome
- Greig cephalopolysyndactyly
- Hydrolethalus syndrome
Treatment Strategies
Multidisciplinary Care
- Pediatric endocrinology
- Neurosurgery
- Orthopedic surgery
- Developmental pediatrics
- Genetic counseling
Surgical Interventions
- Hamartoma resection if indicated
- Polydactyly correction
- Imperforate anus repair
- Cleft palate repair
- Cardiac surgery if needed
Medical Management
- Hormone replacement therapy
- Anticonvulsant medications
- Growth hormone therapy
- Pain management
- Regular monitoring
Supportive Care
- Physical therapy
- Occupational therapy
- Speech therapy
- Educational support
- Psychological support
Genetic Aspects
Molecular Genetics
- GLI3 gene mutations
- Location: chromosome 7p14.1
- Zinc finger protein
- Hedgehog signaling pathway
Inheritance Pattern
- Autosomal dominant
- Variable expressivity
- Complete penetrance
- High rate of de novo mutations
Genetic Testing
- Sequence analysis
- Deletion/duplication analysis
- Prenatal testing options
- Family screening
Genetic Counseling
- Recurrence risk assessment
- Family planning
- Prenatal counseling
- Support group referral
