National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

PHIP-Related disorder


Other Names:
Chung-Jansen syndrome; CHUJANS; Intellectual disability-overweight syndrome caused by PHIP haploinsufficiency; Chung-Jansen syndrome; CHUJANS; Intellectual disability-overweight syndrome caused by PHIP haploinsufficiency; Developmental delay, intellectual disability, obesity, and dysmorphism See More
PHIP-related disorder, also known as Chung-Jansen syndrome, is a rare condition caused by a change in the pleckstrin homology domain-interacting protein (PHIP) gene. The most common signs and symptoms, include mild to severe learning problems, behavior problems, and a tendency toward being overweight.[1][2] PHIP-related disorder is an autosomal dominant condition. This means that a person with the disorder has a 1 in 2 or 50% chance of passing the condition to each child.
Last updated: 4/12/2018
Many people with PHIP-related disorder have mild to severe intellectual disability. People with the disorder who did not have intellectual disability, often have speech problems, global developmental delays in early childhood, and learning problems.[1][2]

Problems with behavior are common. People with PHIP-related disorder and the following behavioral conditions have been reported:[1]

Attention Deficit Hyperactivity Disorder (ADHD)
Features of autism
Problems with impulse control
Aggressive behavior
Mood disorder
Anxiety

In addition to learning and behavior problems, a tendency toward being overweight is common among people with PHIP-realted disorder.[1][2]

People with PHIP-related disorder can have unique physical features, including:[1][2]

High forehead
Full eyebrows with or without hair in between the brows
Upturned nose with thick nostrils
Long spacing between the nose and upper lip
Thin lips
Large ears
Thick helices and earlobes
Tapered fingers
Curved pinky finger
Slight webbing between the second and third toes
Urogenital problems
Vision problems
Differences in skin pigmentation
Fatigue
Last updated: 4/12/2018

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 33 |
Medical Terms Other Names
Learn More:
HPO ID
Percent of people who have these symptoms is not available through HPO
Aggressive behavior
Aggression
Aggressive behaviour
Aggressiveness
[ more ] 		0000718
Anteverted nares
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils
[ more ] 		0000463
Anxiety
Excessive, persistent worry and fear
0000739
Attention deficit hyperactivity disorder
Attention deficit
Attention deficit disorder
Attention deficit-hyperactivity disorder
Attention deficits
Childhood attention deficit/hyperactivity disorder
[ more ] 		0007018
Autosomal dominant inheritance 0000006
Cafe-au-lait spot 0000957
Clinodactyly
Permanent curving of the finger
0030084
Cryptorchidism
Undescended testes
Undescended testis
[ more ] 		0000028
Epicanthus
Eye folds
Prominent eye folds
[ more ] 		0000286
Generalized hypotonia
Decreased muscle tone
Low muscle tone
[ more ] 		0001290
Global developmental delay 0001263
High forehead 0000348
High palate
Elevated palate
Increased palatal height
[ more ] 		0000218
Hypermetropia
Farsightedness
Long-sightedness
[ more ] 		0000540
Hypertelorism
Wide-set eyes
Widely spaced eyes
[ more ] 		0000316
Impulsivity
Impulsive
0100710
Infantile onset
Onset in first year of life
Onset in infancy
[ more ] 		0003593
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Joint hypermobility
Double-Jointed
Flexible joints
Increased mobility of joints
[ more ] 		0001382
Long philtrum 0000343
Macrotia
Large ears
0000400
Micrognathia
Little lower jaw
Small jaw
Small lower jaw
[ more ] 		0000347
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Obesity
Having too much body fat
0001513
Round face
Circular face
Round facial appearance
Round facial shape
[ more ] 		0000311
Short nose
Decreased length of nose
Shortened nose
[ more ] 		0003196
Short philtrum 0000322
Strabismus
Cross-eyed
Squint
Squint eyes
[ more ] 		0000486
Synophrys
Monobrow
Unibrow
[ more ] 		0000664
Tapered finger
Tapered fingertips
Tapering fingers
[ more ] 		0001182
Thick eyebrow
Bushy eyebrows
Dense eyebrow
Heavy eyebrows
Prominent eyebrows
Thick eyebrows
[ more ] 		0000574
Thin vermilion border
Decreased volume of lip
Thin lips
[ more ] 		0000233
Upslanted palpebral fissure
Upward slanting of the opening between the eyelids
0000582
Showing of 33 |
Last updated: 7/1/2020
PHIP-related disorder is a rare condition caused by a genetic change in the pleckstrin homology domain-interacting protein (PHIP) gene. This gene plays an important role in several processes linked to brain and nervous system development. The PHIP gene is also involved in regulating insulin in nervous tissues. To date, PHIP-related disorder is not known to cause diabetes, however people with the disorder are at an increased risk for being overweight which is a risk factor for diabetes.[1][2]
Last updated: 4/12/2018
PHIP-related disorder often occurs for the first time in a family as a new genetic change in the family member with the disorder. However, some cases have been inherited from a parent who has the disorder themselves. People with PHIP-related disorder have a 50% chance of passing the condition on to each child.[1][2]

A few cases of PHIP-related disorder have been caused by a loss of genetic material on chromosome 6, where the PHIP gene is found. These cases are due to a larger change in chromosome 6 versus a change in the PHIP gene alone. These cases may occur for the first time in a family in the family member with the disorder, or be inherited from a parent.[1][2]

Talking with a genetic professional can help a family understand the origin of the PHIP-related disorder in their family, and learn if genetic testing of family members would be helpful.
Last updated: 4/12/2018
The actual prevalence of PHIP-related disorder is not known. To date around 27 cases of PHIP-related disorder have been described in the medical literature.[1][2][3]
Last updated: 4/12/2018

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Social Networking Websites

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 

Selected Full-Text Journal Articles

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  1. Jansen S et al.,. A genotype-first approach identifies an intellectual disability-overweight syndrome caused by PHIP haploinsufficiency. Eur J Hum Genet. 2018 Jan; 26(1):54-63. https://www.ncbi.nlm.nih.gov/pubmed/29209020. Accessed 4/12/2018.
  2. Chung WK et al.,. De novo PHIP-predicted deleterious variants are associated with developmental delay, intellectual disability, obesity, and dysmorphic features. Cold Spring Harb Mol Case Stud. Nov 2016; 2(6):a001172. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5111011/. Accessed 4/12/2018.
  3. de Ligt, J et al.,. Diagnostic exome sequencing in persons with severe intellectual disability. New Eng. J. Med. 2012; 367:1921-1929. http://www.nejm.org/doi/full/10.1056/NEJMoa1206524. Accessed 4/12/2018.