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PubMed This is a summary of 16 peer-reviewed journal articles Updated
Medical Genetics · 18p Deletion Syndrome

The Genetics of 18p Deletion: Understanding the Missing Piece

At a Glance

18p deletion syndrome is caused by a missing piece of DNA on the short arm of chromosome 18. Symptoms depend on which specific genes, like TGIF1 or SMCHD1, are missing. A Chromosomal Microarray (CMA) test is the standard tool used to find the exact size and location of the deletion.

To understand 18p deletion syndrome, it helps to think of your child’s DNA as an instruction manual. Chromosomes are like the volumes of that manual. Your child has the usual number of volumes, but in Volume 18, a portion of the “p arm”—the shorter, top section of the chromosome—is missing [1][2].

The Biology of a “Missing Piece”

Most people have two copies of every chromosome (one from each parent). In 18p deletion syndrome, a child has only one copy of the genes on the short arm of chromosome 18. This state is called hemizygosity [3].

When a gene is hemizygous, the body only has half the usual instructions. For some genes, one copy is enough. For others, the body needs both copies to work correctly. When one copy isn’t enough, it’s called haploinsufficiency, and this is what causes the symptoms of the syndrome [4].

Key Genes and Their Roles

While many genes are located on the 18p arm, researchers have identified a few “key players” that help explain specific symptoms:

  • TGIF1: This gene is vital for early brain development. It helps manage the “Sonic Hedgehog” signaling pathway, which tells the embryonic brain how to divide into two distinct halves [4][5]. When this gene is missing, it can lead to holoprosencephaly (HPE), a condition where the brain doesn’t divide correctly [6].
  • PTPRM: This gene is involved in how cells stick together and communicate. Being missing one copy of PTPRM may make a child more likely to develop autoimmune conditions, where the immune system mistakenly attacks the body [3][7].

Why Every Child is Different

You may meet other families whose children have the same diagnosis but very different symptoms. This happens because the “missing piece” isn’t the same size for everyone. The exact spots where the chromosome broke are called breakpoints [8].

Additionally, genetics is not always a simple “if/then” equation. Some people carry a deletion but show very few symptoms, while others have more complex needs. This is known as phenotypic variability (or incomplete penetrance) [9]. Other factors, like the rest of the child’s genetic makeup or their environment, influence how the deletion affects them [10][11].

How the Diagnosis is Made

Most children are diagnosed using a Chromosomal Microarray (CMA). This is a highly sensitive blood test that scans the entire genome to find missing or extra pieces of DNA [12].

You may have had prenatal screening like NIPT (Noninvasive Prenatal Testing), which looks at the baby’s DNA in the mother’s blood. While NIPT is good at finding some conditions, it often misses smaller deletions like 18p [13][14]. A CMA is the “gold standard” for confirming the exact size and location of the 18p deletion [12][15].

A Note on FSHD Screening

If your child’s deletion is near the very tip (the distal end) of the 18p arm, it may include the loss of the SMCHD1 gene. Missing this specific gene on chromosome 18 can interact with another genetic region (the D4Z4 repeat) on an entirely different chromosome (chromosome 4), increasing the risk for Facioscapulohumeral Muscular Dystrophy (FSHD) [16]. FSHD is a condition that causes muscle weakness in the face and shoulders. Your doctor may recommend a specialized D4Z4 blood test to check for this risk [16].

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Common questions in this guide

What causes the symptoms of 18p deletion syndrome?
Symptoms are caused by haploinsufficiency, which happens when the body only has one copy of the genes on the 18p chromosome arm instead of the usual two. Because the body doesn't have the full set of genetic instructions, it cannot function as expected.
What is the role of the TGIF1 gene in 18p deletion?
The TGIF1 gene is essential for early brain development. If this gene is missing, it can increase the risk of holoprosencephaly, a condition where the brain does not correctly divide into two distinct halves.
Why do children with 18p deletion have different symptoms?
Symptoms vary because the exact size of the missing chromosome piece, known as the breakpoints, differs from child to child. A child's overall genetic makeup and environment also influence how the genetic deletion affects them.
How is 18p deletion syndrome diagnosed?
The condition is most accurately diagnosed using a Chromosomal Microarray (CMA). This highly sensitive blood test scans the entire genome to find the exact size and location of the missing piece of chromosome 18.
Does an 18p deletion increase the risk for muscular dystrophy?
If the genetic deletion includes the SMCHD1 gene near the tip of the chromosome, it can interact with another genetic region and increase the risk for Facioscapulohumeral Muscular Dystrophy (FSHD). Your doctor may recommend a specialized blood test to check for this risk.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Does my child's deletion include the TGIF1 gene, and does this change how we should monitor for brain development?
  2. 2.Does the deletion extend into the distal region where the SMCHD1 gene is located? Do we need to test for FSHD risk?
  3. 3.Can you walk me through the CMA report and show me exactly where the 'breakpoints' are?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (16)
  1. 1

    Spectrum of Movement Disorders in 18p Deletion Syndrome.

    Crosiers D, Blaumeiser B, Van Goethem G

    Movement disorders clinical practice 2019; (6(1)):70-73 doi:10.1002/mdc3.12707.

    PMID: 30746419
  2. 2

    Prenatal diagnosis of de novo monosomy 18p deletion syndrome by chromosome microarray analysis: Three case reports.

    Qi H, Zhu J, Zhang S, et al.

    Medicine 2019; (98(14)):e15027 doi:10.1097/MD.0000000000015027.

    PMID: 30946338
  3. 3

    Monozygotic triplets with juvenile-onset autoimmunity and 18p microdeletion involving PTPRM.

    Herlin MK, Bernth Jensen JM, Andreasen L, et al.

    Frontiers in genetics 2024; (15()):1437566 doi:10.3389/fgene.2024.1437566.

    PMID: 39359478
  4. 4

    Functions of TGIF homeodomain proteins and their roles in normal brain development and holoprosencephaly.

    Wotton D, Taniguchi K

    American journal of medical genetics. Part C, Seminars in medical genetics 2018; (178(2)):128-139 doi:10.1002/ajmg.c.31612.

    PMID: 29749689
  5. 5

    Genetic and Molecular Analyses indicate independent effects of TGIFs on Nodal and Gli3 in neural tube patterning.

    Taniguchi K, Anderson AE, Melhuish TA, et al.

    European journal of human genetics : EJHG 2017; (25(2)):208-215 doi:10.1038/ejhg.2016.164.

    PMID: 27924807
  6. 6

    Deletion 18p11.32p11.31 in a Child with Global Developmental Delay and Atypical, Drug-Resistant Absence Seizures.

    Verrotti A, Palka C, Prezioso G, et al.

    Cytogenetic and genome research 2015; (146(2)):115-119 doi:10.1159/000438502.

    PMID: 26278570
  7. 7

    18p Deletion Syndrome Associated with Type 1 Diabetes and Hashimoto's Thyroiditis: A Case Report on Autoimmune Disorders and Genetic Factors.

    Oktay MA, Tunca Küçükali ET, Kılınç Uğurlu A, et al.

    Journal of clinical research in pediatric endocrinology 2025; doi:10.4274/jcrpe.galenos.2025.2025-6-5.

    PMID: 41194499
  8. 8

    The genotype and phenotype of chromosome 18p deletion syndrome: Case series.

    Jin Q, Qiang R, Cai B, et al.

    Medicine 2021; (100(18)):e25777 doi:10.1097/MD.0000000000025777.

    PMID: 33950970
  9. 9

    [Genetic analysis of a fetus with partial 18p deletion].

    Chen X, Zhu Y, Zhang W, Yan W

    Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 2021; (38(5)):477-480 doi:10.3760/cma.j.cn511374-20200417-00278.

    PMID: 33974260
  10. 10

    Intellectual, adaptive and behavioural characteristics in four patients with 18p deletion syndrome.

    Mello CB, Bueno OFA, Benedetto LM, et al.

    Journal of intellectual disability research : JIDR 2019; (63(3)):225-232 doi:10.1111/jir.12568.

    PMID: 30536814
  11. 11

    18p Deletion Syndrome With Concurrent Frizzled-4 Mutation: Surgical Management of Bilateral Stage 5 Traction Retinal Detachment.

    Wakabayashi T, Patel SN, Starr MR, Yonekawa Y

    Ophthalmic surgery, lasers & imaging retina 2023; (54(5)):284-290 doi:10.3928/23258160-20230307-02.

    PMID: 37022334
  12. 12

    De Novo Interstitial Deletion of 9q in a Pediatric Patient With Global Developmental Delay.

    Keselman D, Singh R, Cohen N, Fefer Z

    Child neurology open 2019; (6()):2329048X19844920 doi:10.1177/2329048X19844920.

    PMID: 31106228
  13. 13

    Evaluation of the clinical utility of extended non-invasive prenatal testing in the detection of chromosomal aneuploidy and microdeletion/microduplication.

    Tian W, Yuan Y, Yuan E, et al.

    European journal of medical research 2023; (28(1)):304 doi:10.1186/s40001-023-01285-2.

    PMID: 37644576
  14. 14

    Chromosomal abnormalities not currently detected by cell-free fetal DNA: a retrospective analysis at a single center.

    Shani H, Goldwaser T, Keating J, Klugman S

    American journal of obstetrics and gynecology 2016; (214(6)):729.e1-729.e11.

    PMID: 26721783
  15. 15

    Clinically significant findings in a decade-long retrospective study of prenatal chromosomal microarray testing.

    Olayiwola JO, Marhabaie M, Koboldt D, et al.

    Molecular genetics & genomic medicine 2024; (12(3)):e2349 doi:10.1002/mgg3.2349.

    PMID: 38263869
  16. 16

    Monosomy 18p is a risk factor for facioscapulohumeral dystrophy.

    Balog J, Goossens R, Lemmers RJLF, et al.

    Journal of medical genetics 2018; (55(7)):469-478 doi:10.1136/jmedgenet-2017-105153.

    PMID: 29563141

This page explains the genetics of 18p deletion syndrome for educational purposes only. Always consult a genetic counselor or medical geneticist for help interpreting your child's specific test results and planning their care.

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