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Disease Profile

PACS1-related syndrome

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)

Autosomal dominant intellectual disability-17; Intellectual disability-craniofacial dysmorphism-cryptorchidism syndrome; Schuurs-Hoeijmakers syndrome;

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

PACS-1 related syndrome causes intellectual disabilitydevelopmental delay, and distinctive facial features. This condition is present from birth. Symptoms of PACS-1 related syndrome may include low muscle tone, feeding difficulties, constipation, seizures, and heart defects. PACS1-related syndrome is caused by a specific genetic variant in the PACS1 gene. In most cases, this gene variant is not inherited, but occurs as a new change during the making of the egg or the sperm. The diagnosis is based on the symptoms, a clinical examination, and may be confirmed by the results of genetic testing. As of 2017, less than 70 people have been diagnosed with this syndrome. Treatment for PACS1-related syndrome is focused on managing the symptoms and may include medications to prevent seizures and placement of a feeding tube to help with weight gain.[1][2][3][4]

Symptoms

The following list includes the most common signs and symptoms in people with PACS1-related syndrome. These features may be different from person to person. Some people may have more symptoms than others, and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition.

Signs and symptoms of PACS1-related syndrome may include:[1][3][4]

  • Intellectual disability
  • Developmental delay
  • Low muscle tone (hypotonia)
  • Feeding difficulties
  • Seizures
  • Behavioral features
  • Distinctive facial features
  • Heart defects

Children with PACS1-related syndrome often have facial features that make them look similar to each other. These features can include low hairline, low set ears, wide spaced eyes, and a round nasal tip. Some boys with PACS1-related syndrome may have undescended testes (cryptorchidism). Less than 70 cases of PACS1-related syndrome have been reported in the medical literature, and little is known about how this condition changes over time.[3]

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
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 ]

Cause

PACS1-related syndrome occurs when the PACS1 gene is not working correctly. DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.[3]

Diagnosis

Diagnosis of PACS1-related syndrome is based on the symptoms, a clinical examination, and may confirmed by the results of genetic testing. Other conditions may need to be ruled out before PACS1-related syndrome is diagnosed.[3][4]

Treatment

Treatment of PACS1-related syndrome is focused on managing the symptoms. Treatment options may include medications for seizures, placement of a feeding tube, and surgery to correct heart defects.[2][3]

Specialists involved in the care of someone with PACS1-related syndrome may include:

  • Neurologist
  • Gastroenterologist
  • Cardiologist
  • Ophthalmologist
  • Developmental specialist
  • Physical and/or occupational therapist
  • Medical geneticist

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.

Organizations Supporting this Disease

    Social Networking Websites

    • Visit the PACS1 private family support group on Facebook.

    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.

    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.

        References

        1. Schuurs-Hoeijmakers Syndrome; SHMS. Online Mendelian Inheritance in Man. August 17, 2016; https://www.omim.org/entry/615009.
        2. 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.
        3. Lusk L, Smith S, Martin C, Taylor C, Chung W. PACS1 Neurodevelopmental Disorder. GeneReviews. July 16, 2020; https://ncbi.nlm.nih.gov/books/NBK559434.
        4. Seto MT, Bertoli-Avella AM, Cheung KW, Chan KY, Yeung KS, Fung JL, et al. Prenatal and postnatal diagnosis of Schuurs-Hoeijmakers syndrome: Case series and review of the literature.. Am J Med Genet A. Nov 9, 2020; Epub ahead of print. https://pubmed.ncbi.nlm.nih.gov/33166031/.
        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.

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