Rare Immunology News

Disease Profile

PHIP-Related disorder

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

#N/A

ICD-10

#N/A

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Chung-Jansen syndrome; CHUJANS; Intellectual disability-overweight syndrome caused by PHIP haploinsufficiency;

Summary

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.

Symptoms

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

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.

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

Cause

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]

Organizations

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

Learn more

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

References

  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. https://www.nejm.org/doi/full/10.1056/NEJMoa1206524. Accessed 4/12/2018.

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