Chung-Jansen Syndrome: Symptoms, Causes, Diagnosis, and Management

Chung-Jansen syndrome, also known as PHIP-related disorder, is a rare genetic condition that can affect development, learning, behaviour, growth, and physical health. It is caused by a disease-causing change in the PHIP gene, which plays a role in cell growth and brain development. 

Common features may include developmental delay, learning difficulties, intellectual disability, low muscle tone, behavioral differences, and an increased tendency toward overweight or obesity. However, the symptoms and level of support needed can vary considerably from one person to another. 

As access to genetic testing has increased, more people with Chung-Jansen syndrome have been identified. Early diagnosis can help families access appropriate developmental services, medical monitoring, educational support, and genetic counseling

What Is Chung-Jansen Syndrome? 

Chung-Jansen syndrome is a rare neurodevelopmental disorder caused by a pathogenic or likely pathogenic variant in one copy of the PHIP, or Pleckstrin Homology Domain Interacting Protein, gene. 

The PHIP gene is involved in processes related to cell growth, energy regulation, and brain development. Changes affecting this gene may influence learning, behavior, movement, communication, and physical growth. 

The condition is also called PHIP-related disorder. Researchers continue to learn more about its features and long-term effects as additional individuals are diagnosed worldwide. Because it has only recently been recognized as a distinct genetic syndrome, information about adulthood and long-term outcomes remains limited. 

Symptoms of Chung-Jansen Syndrome 

The signs and symptoms of Chung-Jansen syndrome vary widely. Not every person will experience all of the features listed below. 

Developmental and Learning Differences 

Children may experience: 

  • Delayed sitting, crawling, standing, or walking 
  • Speech and language delay 
  • Learning difficulties 
  • Intellectual disability, which may vary in severity 
  • Delayed fine and gross motor skills 
  • Difficulties with coordination, balance, or daily living skills 

A child’s abilities may vary across communication, motor development, learning, and practical skills. Individualized developmental assessment can help identify areas of strength and areas where additional support may be helpful. 

Behavioral and Emotional Features 

Behavioral and emotional differences may include: 

  • Attention-deficit/hyperactivity disorder or attention-related difficulties 
  • Anxiety 
  • Impulsivity 
  • Aggression or behavioral dysregulation 
  • Difficulty regulating emotions 
  • Sleep-related concerns in some individuals 

Not every child develops these features, and behavioral needs may change with age. 

Movement and Muscle Tone 

Some children may have: 

  • Delayed motor milestones 
  • Reduced stamina 
  • Coordination or balance difficulties 
  • An unusual walking pattern  

Physical and occupational therapy may be recommended based on the child’s individual needs. 

Physical Characteristics 

Some individuals with Chung-Jansen syndrome share certain physical characteristics, including: 

  • Full, thick, or prominent eyebrows 
  • A small or upturned nose 
  • Large ears or thick, fleshy earlobes 
  • A full lower lip 
  • Tapered fingers 
  • Curvature of the fifth finger, known as clinodactyly 

These features vary widely and are not present in everyone. Facial or physical characteristics alone are not enough to diagnose the condition. 

Other Health Concerns 

Some individuals may also experience: 

  • Feeding difficulties during infancy 
  • Constipation or other gastrointestinal concerns 
  • Vision problems 
  • Fatigue or reduced endurance 
  • Overweight or obesity during childhood or adolescence 
  • Less commonly reported kidney, skeletal, or other congenital differences 

Regular medical follow-up can help identify and manage concerns based on the individual’s symptoms. 

What Causes Chung-Jansen Syndrome? 

Chung-Jansen syndrome is caused by a pathogenic or likely pathogenic variant in the PHIP gene. 

In many individuals, the genetic change occurs de novo, meaning it develops for the first time in the affected person and is not inherited from either parent. 

In some families, the condition follows an autosomal dominant inheritance pattern. This means that a parent with a disease-causing PHIP variant can pass it to a child. If a parent has the variant, each pregnancy has a 50% chance of inheriting it. 

Nothing a parent did before or during pregnancy causes Chung-Jansen syndrome. 

When the variant appears to be de novo, the chance of recurrence in another pregnancy is generally low, although it may not be zero. A genetic counselor can provide information specific to the family. 

How Is Chung-Jansen Syndrome Diagnosed? 

Because its symptoms overlap with those of many other developmental and genetic conditions, Chung-Jansen syndrome usually cannot be diagnosed based on physical or behavioral features alone. 

Evaluation may include: 

  • A detailed medical and developmental history 
  • Physical and neurological examinations 
  • Developmental, behavioral, or educational assessments 
  • Review of the family medical history 
  • Genetic testing 

Genetic testing may include: 

  • A multigene panel 
  • Exome sequencing 
  • Genome sequencing 
  • Chromosomal microarray 

Chromosomal microarray may identify a deletion involving the PHIP gene, while sequencing tests may identify disease-causing changes within the gene itself. 

Diagnosis is generally confirmed when testing identifies a pathogenic or likely pathogenic PHIP variant, or a deletion involving the PHIP gene, that is consistent with the person’s clinical features. A variant of uncertain significance does not usually confirm the diagnosis on its own. 

A confirmed genetic diagnosis can help guide medical monitoring, developmental support, educational planning, and genetic counseling. 

Management and Support 

There is currently no cure or syndrome-specific treatment for Chung-Jansen syndrome. Care focuses on supporting development, addressing symptoms, and monitoring associated health concerns. 

A personalized care plan may include: 

  • Speech and language therapy 
  • Physical therapy 
  • Occupational therapy 
  • Behavioral or psychological support 
  • Special education services 
  • An individualized education program, or IEP 
  • Nutritional guidance and healthy-weight monitoring 
  • Regular eye examinations 
  • Developmental and behavioral assessments 
  • Routine medical follow-up 

Children with seizures, unusual movements, regression, or other neurological concerns may be referred to a neurologist. 

Early intervention services may support communication, mobility, learning, and daily living skills according to the child’s individual needs. 

Because the condition can affect several areas of health and development, care may involve a multidisciplinary team. 

Living With Chung-Jansen Syndrome 

People with Chung-Jansen syndrome may continue to make developmental progress throughout childhood, adolescence, and adulthood. 

Support needs vary. Some individuals may develop greater independence over time, while others may require ongoing assistance with education, communication, health, behavior, or daily living activities. 

Helpful supports can include: 

  • Individualized educational accommodations 
  • Communication support 
  • Occupational and physical therapy 
  • Behavioral and emotional support 
  • Healthy-weight monitoring 
  • Transition planning for adulthood 
  • Family and community support 

Regular follow-up with developmental pediatricians, geneticists, neurologists, psychologists, therapists, and other specialists can help address changing needs over time. 

Frequently Asked Questions 

What are the symptoms of Chung-Jansen syndrome? 

Symptoms vary from person to person. Common features include developmental delay, speech and language delay, learning difficulties, intellectual disability, low muscle tone, motor delays, behavioral differences, feeding difficulties, constipation, vision problems, and an increased tendency toward overweight or obesity. 

Some individuals have physical characteristics such as thick eyebrows, an upturned nose, large ears or earlobes, tapered fingers, or a curved fifth finger. 

What causes Chung-Jansen syndrome? 

Chung-Jansen syndrome is caused by a pathogenic or likely pathogenic variant in the PHIP gene. In many cases, the genetic change occurs de novo, meaning it is not inherited from either parent. In other cases, it may be inherited from an affected parent. 

Is Chung-Jansen syndrome inherited? 

Most affected individuals are the first person in their family known to have the condition. However, Chung-Jansen syndrome can be inherited in an autosomal dominant pattern. 

If a parent has the disease-causing PHIP variant, each pregnancy has a 50% chance of inheriting it. A genetic counselor can explain the recurrence risk for a specific family. 

What are the facial features of Chung-Jansen syndrome? 

Some individuals may have full or thick eyebrows, a small or upturned nose, large ears with thick or fleshy earlobes, or a full lower lip. 

These features are variable and may be subtle. Not everyone with Chung-Jansen syndrome has the same appearance, and facial features alone cannot confirm the condition. Diagnosis requires clinical evaluation and genetic testing. 

How is Chung-Jansen syndrome diagnosed? 

Diagnosis usually involves clinical evaluation and genetic testing. Testing may include a multigene panel, exome sequencing, genome sequencing, or chromosomal microarray. 

A diagnosis is typically confirmed when testing identifies a pathogenic or likely pathogenic variant, or a deletion involving the PHIP gene, that is consistent with the person’s clinical features. 

Is there a cure for Chung-Jansen syndrome? 

There is currently no cure or syndrome-specific treatment. Management focuses on supporting development, addressing medical and behavioral concerns, and providing appropriate therapies and educational services. 

Medical Disclaimer: This article is intended for educational purposes only and should not replace professional medical advice, diagnosis, or treatment. If you have concerns about your child’s development or genetic health, consult a qualified healthcare provider or genetic specialist. 

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