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

PACS1-related syndrome


Other Names:
Autosomal dominant intellectual disability-17; Intellectual disability-craniofacial dysmorphism-cryptorchidism syndrome; Schuurs-Hoeijmakers syndrome; Autosomal dominant intellectual disability-17; Intellectual disability-craniofacial dysmorphism-cryptorchidism syndrome; Schuurs-Hoeijmakers syndrome; SHMS See More
Categories:
PACS-1 related syndrome is characterized by intellectual disability, developmental delay, and mildly distinctive facial features. People with this syndrome may also have seizures, difficulty eating and gaining weight, and autism.[1] As of 2017, less than 70 people have been diagnosed with this syndrome. However, since the first cases of the syndrome were only published in the medical journals in 2012, the number of children and adults found to have the syndrome may increase.[2][3] 

PACS1-related syndrome is caused by a specific change or mutation in the PACS1 gene. So far, this genetic change has not been found in the parents of a child with PACS1 -related syndrome. This means the change in the PACS1 gene most likely happened during the making of the egg  or the sperm. PACS1-related disorder is suspected when a doctor sees signs of the syndrome such as intellectual disability and the characteristic facial features. Genetic testing of the PACS1 gene is needed to confirm the diagnosis.[1] Treatment for PACS1-related syndrome depends on the signs and symptoms each person has, but may include medications to prevent seizures, and speech, physical, and occupational therapies.[2][3][4]
Last updated: 10/7/2017
Signs of PACS1-related syndrome include intellectual disability, developmental delay, and mild distinctive facial features causing those who have the syndrome to look a lot alike. The typical facial features include having a low hairline on the forehead, eyes that are spaced far apart (hypertelorism) and slanting downwards, thick eyebrows that may be connected to each other, long eyelashes, large ears that are set low on the head, and gaps between the teeth.[1] 

Children with PACS1-related syndrome may have speech delay and low muscle tone (hypotonia). Babies with the syndrome may also have certain problems that are present from birth (congenital) including abnormalities of the heart, brain, eyes, or kidneys. Some boys with PACS1-related syndrome may have undescended testes (cryptorchidism). People with PACS1-related syndrome may have other features including near-sightedness (myopia), seizures, difficulty eating, and autism.[1][2] 
Last updated: 10/7/2017

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 70 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal facial shape
Unusual facial appearance
0001999
Global developmental delay 0001263
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
30%-79% of people have these symptoms
Abnormal temper tantrums 0025160
Bilateral ptosis
Drooping of both upper eyelids
0001488
Bulbous nose 0000414
Constipation 0002019
Cryptorchidism
Undescended testes
Undescended testis
[ more ] 		0000028
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
Failure to thrive
Faltering weight
Weight faltering
[ more ] 		0001508
Highly arched eyebrow
Arched eyebrows
Broad, arched eyebrows
High, rounded eyebrows
High-arched eyebrows
Thick, flared eyebrows
[ more ] 		0002553
Hypertelorism
Wide-set eyes
Widely spaced eyes
[ more ] 		0000316
Infantile muscular hypotonia
Decreased muscle tone in infant
0008947
Long eyelashes
Increased length of eyelashes
Unusually long eyelashes
[ more ] 		0000527
Low-set ears
Low set ears
Lowset ears
[ more ] 		0000369
Oral aversion 0012523
Protruding ear
Prominent ear
Prominent ears
[ more ] 		0000411
5%-29% of people have these symptoms
Abnormal cardiac septum morphology 0001671
Abnormal renal morphology
Abnormally shaped kidney
Kidney malformation
Kidney structure issue
Structural kidney abnormalities
[ more ] 		0012210
Absent speech
Absent speech development
Lack of language development
Lack of speech
No speech development
No speech or language development
Nonverbal
[ more ] 		0001344
Autistic behavior 0000729
Bicuspid aortic valve
Aortic valve has two leaflets rather than three
0001647
Broad thumb
Broad thumbs
Wide/broad thumb
[ more ] 		0011304
Cavum septum pellucidum 0002389
Cerebellar atrophy
Degeneration of cerebellum
0001272
Cerebellar hypoplasia
Small cerebellum
Underdeveloped cerebellum
[ more ] 		0001321
Clinodactyly of the 5th finger
Permanent curving of the pinkie finger
0004209
Coloboma
Notched pupil
0000589
Decreased serum complement C3 0005421
Diastema
Gap between teeth
0000699
Downturned corners of mouth
Downturned corners of the mouth
Downturned mouth
[ more ] 		0002714
Dysarthria
Difficulty articulating speech
0001260
Focal emotional seizure with laughing 0010821
Gastroesophageal reflux
Acid reflux
Acid reflux disease
Heartburn
[ more ] 		0002020
Inguinal hernia 0000023
Low anterior hairline
Low frontal hairline
Low-set frontal hairline
[ more ] 		0000294
Macrotia
Large ears
0000400
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ] 		0000252
Nasogastric tube feeding 0040288
Partial absence of cerebellar vermis 0002951
Patent ductus arteriosus 0001643
Patent foramen ovale 0001655
Pectus excavatum
Funnel chest
0000767
Pes planus
Flat feet
Flat foot
[ more ] 		0001763
Scoliosis 0002650
Single transverse palmar crease 0000954
Single umbilical artery
Only one artery in umbilical cord instead of two
0001195
Slender finger
Narrow fingers
Slender fingers
thin fingers
[ more ] 		0001238
Smooth philtrum 0000319
Synophrys
Monobrow
Unibrow
[ more ] 		0000664
Thin upper lip vermilion
Thin upper lip
0000219
Umbilical hernia 0001537
Unsteady gait
Unsteady walk
0002317
Ventricular septal defect
Hole in heart wall separating two lower heart chambers
0001629
Wide intermamillary distance
Wide-spaced nipples
Widely spaced nipples
Widely-spaced nipples
[ more ] 		0006610
Wide mouth
Broad mouth
Large mouth
[ more ] 		0000154
Percent of people who have these symptoms is not available through HPO
Aggressive behavior
Aggression
Aggressive behaviour
Aggressiveness
[ more ] 		0000718
Autosomal dominant inheritance 0000006
Delayed speech and language development
Deficiency of speech development
Delayed language development
Delayed speech
Delayed speech acquisition
Delayed speech development
Impaired speech and language development
Impaired speech development
Language delay
Language delayed
Language development deficit
Late-onset speech development
Poor language development
Speech and language delay
Speech and language difficulties
Speech delay
[ more ] 		0000750
Feeding difficulties
Feeding problems
Poor feeding
[ more ] 		0011968
Generalized hypotonia
Decreased muscle tone
Low muscle tone
[ more ] 		0001290
Large hands
large hand
0001176
Long foot
Disproportionately large feet
large feet
long feet
[ more ] 		0001833
Myopia
Close sighted
Near sighted
Near sightedness
Nearsightedness
[ more ] 		0000545
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Ptosis
Drooping upper eyelid
0000508
Seizure 0001250
Speech apraxia 0011098
Strabismus
Cross-eyed
Squint
Squint eyes
[ more ] 		0000486
Volvulus 0002580
Showing of 70 |
Last updated: 7/1/2020
PACS1-related syndrome is caused by a specific change or mutation in the PACS1 gene. The PACS1 gene acts like a blueprint and tells cells how to make the PACS1 protein. The PACS1 protein is found in the membrane of the Golgi apparatus.[3][4][5] The Golgi apparatus acts as the shipping and packing department of a cell. It modifies other proteins to prepare them to be shipped to other parts of the cell or outside of the cell.[6] Scientists believe the job of the PACS1 protein is to help get proteins into and/or out of the Golgi apparatus. Scientists also know that cells make a lot more PACS1 protein during the development of the brain and make very little of the protein after birth. Scientists are working to understand how the ability of the PACS1 protein to do its job is changed in cells of people with PACS1-related syndrome.[3][4][5]
Last updated: 10/7/2017
PACS1-related syndrome is an autosomal dominant syndrome.[1] This means that only one copy of the PACS1 gene must be changed in each cell of the body in order for a person to have signs and symptoms of the syndrome. Remember, genes come in pairs (two copies) and one copy is inherited from each birth parent.

In every case of PACS1-related syndrome that has been found so far, the change in PACS1 gene is new and not found in either parent.[2][3] This means that the genetic change was not passed down from either the mother or the father, but instead occurred for the first time (de novo) in the child who has the syndrome. In other words, the change in the PACS1 gene happened by mistake during the making of the egg or the sperm.

If two parents have a child who has PACS1-related syndrome and neither parent has the change in their own copies of the PACS1 gene, the chances that the parents will have another child with PACS1-related syndrome is less than 1%. People with PACS1-related syndrome have not been known to have children so far. Theoretically, if someone with the syndrome were to have children, there would be a 50% chance for each child to have PACS1-related syndrome as well.[2][3] 
Last updated: 10/7/2017
PACS1-related syndrome may be suspected when a doctor notices signs and symptoms that are commonly found in children or adults who have the syndrome, such as intellectual disability and mildly distinctive facial features.  The diagnosis is confirmed by finding the specific change in the PACS1 gene through genetic testing. In many cases, the doctor may not initially suspect PACS1-related syndrome because the syndrome is so rare and most of the signs and symptoms are not unique to this syndrome. Therefore, PACS1-related syndrome is frequently diagnosed with a very broad genetic test called whole exome sequencing.[3][4]
Last updated: 10/7/2017
The treatment of PACS1-related syndrome  depends on the signs and symptoms present in each person. When a child or adult is first diagnosed with PACS1-related syndrome, a number of tests and consultations may be recommended including:[2][4] 
  • Meeting with a dietician to discuss any feeding problems
  • EEG to assess if there are any seizures occurring
  • Brain MRI to look for any brain abnormalities
  • Consultation with an ophthalmologist to assess for any eye abnormalities
  • Ultrasound of heart and kidneys.
Although there is no cure for PACS1-related syndrome, there are treatment and therapy options that can help manage many of the signs and symptoms of the syndrome. Anti-epileptic medications can be used to help control seizures. Sometimes, children with PACS1-related syndrome may need feeding tubes to help them get enough nutrients. Children with PACS1-related syndrome may be recommended to be followed by a developmental pediatrician, and they may benefit from speech, physical, and occupational therapy. Some children and adults with PACS1-related syndrome are better able to communicate if they learn sign language or have an electronic device to help them communicate.[2][3][4]
Last updated: 10/7/2017
Because PACS1-related syndrome is so rare, there is not a lot of information about the long-term outlook for children and adults with the syndrome. PACS1-related syndrome is not known to shorten a person’s lifespan.[3] People with PACS1-related syndrome will likely need extra help in school, such as special education classes. They will also need to be monitored throughout their lives to make sure they do not develop any additional health issues.[2] 
Last updated: 10/7/2017

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

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Patient Registry

  • A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with PACS1-related syndrome. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

    Registries for PACS1-related syndrome:
    Simons SearchLight
     

General Clinical Trials & Research

  • The PACS1 Syndrome Research Foundation is a private foundation dedicated to finding a cure for PACS1 syndrome by actively funding innovative scientific research. The foundation has 2 founding trustees (parents of a child with PACS1 syndrome) who are also the donors. All funding decisions are scientifically validated and made by the founding trustees based on recommendations and consensus from their Scientific Advisory Team.

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.

Organizations Supporting this Disease

Social Networking Websites

  • Visit the PACS1 private family support group on Facebook.

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.

Where to Start

  • The Simons Variation in Individuals Project is an online community that supports families with rare genetic changes (also called "genomic variants") associated with features of autism and developmental delay. Simons VIP Connect provides access to resources, information, and family support. They also provide an opportunity for families to participate in research. Click on the link to access information about the PACS1 gene.
  • Unique is a source of information and support for families and individuals affected by rare chromosome disorders. Click on the link to view information about PACS1-related syndrome.

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. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss PACS1-related syndrome. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • Is there a way that I can find out where other families with PACS1-related syndrome are located? See answer


  1. Schuurs-Hoeijmakers Syndrome; SHMS. Online Mendelian Inheritance in Man. August 17, 2016; https://www.omim.org/entry/615009.
  2. Schuurs J and Brunner H. PACS1 related syndrome. Unique: The Rare Chromosome Disorder Support Group. 2016; http://www.rarechromo.org/information/Chromosome%2011/PACS1%20related%20syndrome%20FTNW.pdf.
  3. About PACS1. PACS1 Families. https://pacs1families.wordpress.com/about/. Accessed 9/27/2017.
  4. Shurrs-Hoeijmakers JH, Landsverk ML, Foulds N, Kukolich MK, Gavrilova RH, Greville-Heygate S, Hanson-Kahn A, Bernstein JA, Glass J, Chitayat D, Burrow TA, Husami A, Collins K, and Wusik K. Clinical delineation of the PACS1-related syndrome—Report on 19 patients. American Journal of Medical Genetics Part A. March 2016; 170(3):670-675. https://www.ncbi.nlm.nih.gov/pubmed/26842493.
  5. Schuurs-Hoeijmakers JH, Oh EC, Vissers LE, Swinkels ME, Gilissen C, Willemsen MA, Holvoet M, Steehouwer M, Veltman JA, de Vries BB, van Bokhoven H, de Brouwer AP, Katsanis N, Devriendt K, Brunner HG. Recurrent de novo mutations in PACS1 cause defective cranial-neural-crest migration and define a recognizable intellectual-disability syndrome. Am J Hum Genet. December 7, 2012; 91(6):1122-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3516611.
  6. Davidson MS. Golgi Apparatus. Florida State University: Molecular Expressions. November 13, 2015; https://micro.magnet.fsu.edu/cells/golgi/golgiapparatus.html.