18q Deletion Syndrome

What Is 18q Deletion Syndrome? | A Designated Intractable Disease Caused by Deletion on Chromosome 18’s Long Arm

18q deletion syndrome is a congenital chromosomal disorder caused by the loss of the region spanning 18q21 to the terminal end (qter) on the long arm of chromosome 18 (the longer of its two arms, known as 18q). This region contains multiple genes, and exactly which portion is missing determines the combination and severity of symptoms in each individual. Let’s start by looking at the condition as a whole.

In Japan, 18q deletion syndrome is treated as one of the 11 conditions that make up Designated Intractable Disease 139, “Congenital Hypomyelinating Leukoencephalopathy.” This is an umbrella term for disorders in which myelin — the sheath that covers the nerve fibers of the brain — fails to form properly. In 18q deletion syndrome, deletion of the MBP gene (discussed below) is thought to be the main cause of this hypomyelination.

How Rare Is This Condition?

Domestic and international reports put the incidence of 18q deletion syndrome at roughly 1 in 40,000 to 55,000 births. The figures vary between studies because the deleted region they examine differs — some look at the entire long arm, while others focus on a specific segment. According to the Japan Intractable Diseases Information Center, the total number of patients certified for medical assistance under Designated Disease 139 (all 11 conditions combined) is around 200 nationwide, and 18q deletion syndrome is one of the subtypes within that group.

Looking at the numbers alone, this condition may feel distant and unfamiliar. But it’s precisely because it’s so rare that accurate information can be hard to find. In this article, we’ve drawn on information from public institutions and academic sources to organize what is currently known.

Causes | Deletion of 18q21→qter and the MBP and TCF4 Genes

The cause is loss of the region spanning 18q21 to qter on the long arm of chromosome 18, and the specific genes included in the deleted region determine which symptoms appear. Two genes are considered especially significant: the MBP (myelin basic protein) gene near 18q23, and the TCF4 gene near 18q21.2.

The MBP gene works to build myelin, the sheath that covers the nerve fibers of the brain. When this gene is included in the deletion, myelin is not produced sufficiently, which is thought to lead to hypomyelination — visible on MRI as high-signal areas in the brain’s white matter. The TCF4 gene, when included in the deleted region, can produce features that closely resemble Pitt-Hopkins syndrome, such as intellectual disability and characteristic facial features.

This condition follows an autosomal dominant inheritance pattern. Most cases arise from a spontaneous, sporadic new mutation (de novo), but in rare cases, one parent carries a balanced translocation — a rearrangement in which parts of chromosomes have swapped places without any net gain or loss of genetic material. Parents who carry a balanced translocation themselves almost always show no symptoms.

In my own genetic counseling practice, I have repeatedly met parents who blame themselves, wondering whether something in their daily life during pregnancy might have caused this. But apart from a balanced translocation, nothing about how a pregnancy is spent or a parent’s lifestyle habits causes this condition. If you’re considering a future pregnancy, parental chromosome testing can clarify the situation. If you have concerns, please consult a specialist through genetic counseling.

Main Symptoms | Developmental Delay, Hearing Loss, Hypomyelination, and More

The main symptoms include developmental delay, intellectual disability, hearing loss, low muscle tone, and hypomyelination, and both how they present and how severe they are vary greatly from person to person. Not everyone shows every symptom. Here is an overview of the most representative ones.

• Developmental delay / intellectual disability: Motor and language development progress slowly, typically in the mild-to-moderate range.
• Hypomyelination: High-signal areas appear in the brain’s white matter on MRI, believed to be linked to deletion of the MBP gene.
• Hearing loss: Conductive hearing loss caused by a narrow or closed ear canal, sometimes accompanied by sensorineural hearing loss as well.
• Low muscle tone / coordination difficulties: Muscle tone is reduced, which can make movements appear awkward or uncoordinated.
• Growth failure: Short stature is common and may be accompanied by growth hormone deficiency.
• Characteristic facial and skeletal features: Midface hypoplasia, nystagmus, cleft palate, and limb deformities may be observed.

In addition, seizures and microcephaly have also been reported. When the deletion extends to include the TCF4 gene, mood fluctuations and autism spectrum traits are also reported to appear more strongly. The exact combination of symptoms truly differs from person to person.

About 3q13.31 Deletion Syndrome

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Diagnostic Criteria and the Path to a Definitive Diagnosis | G-Banding, FISH, and MRI Findings

Diagnosis is confirmed by combining clinical symptoms such as growth failure and developmental delay, abnormal white matter findings on MRI, and confirmation of the 18q21→qter deletion through chromosome testing (G-banding and FISH). Under the diagnostic criteria for Designated Disease 139, the assessment is based mainly on the following four items.

The first is growth failure, particularly short stature. The second is developmental delay. The third is the presence of pathological high-signal areas in the brain’s white matter on MRI. The fourth is confirmation, through G-banding chromosome analysis and FISH, of a deletion on the long arm of chromosome 18 (18q21→qter). Diagnosis is made by weighing all of these together.

Several scales, including the Cailloux classification, are used to assess symptom severity. Because a certain level of severity must be met to receive medical expense assistance as a designated intractable disease, please confirm the detailed criteria with your treating physician or your medical institution’s consultation desk.

Test	Classification	Coverage for 18q Deletion Syndrome	Physical Burden
Basic NIPT (trisomy 13, 18, 21)	Non-definitive (screening) test	Not covered (targets numerical chromosome abnormalities only)	Blood draw only
Amniocentesis + chromosome analysis (G-banding, FISH)	Definitive test	Can confirm the exact extent of the deletion	Miscarriage risk of roughly 0.3%
Chorionic villus sampling (CVS) + chromosome analysis	Definitive test	Can confirm the diagnosis early in pregnancy	Miscarriage risk of roughly 1%
Postnatal blood test (chromosome analysis)	Definitive test	Can confirm the diagnosis after birth	Blood draw only

Can NIPT Detect It? | Not Covered by Basic Panels, Included in Expanded Panels

18q deletion syndrome is not covered by basic NIPT (trisomy 13, 18, and 21) or the basic 23-condition microdeletion panel, but it is included as a target condition in expanded panels that screen a broader range of the genome. When considering testing, it’s important to understand this difference in scope.

Taking Hiro Clinic NIPT as an example, the 23-condition microdeletion/duplication panel associated with intellectual disability does not include 18q deletion syndrome. However, the 116-condition microdeletion/duplication panel based on whole-genome analysis does include 18q deletion syndrome as one of its target conditions. When choosing a test, be sure to check the full list of covered conditions.

One important point not to misunderstand: even if an expanded panel returns a “positive” or “possible” result, this alone does not confirm a diagnosis. NIPT is strictly a non-definitive screening test, and a definitive diagnosis requires chromosome analysis by amniocentesis (G-banding and FISH). It is not a test that can guarantee unlimited accuracy.

How It Differs from Trisomy 18 (Edwards Syndrome) and 18p Deletion Syndrome

18q deletion syndrome is a distinct condition from trisomy 18 (Edwards syndrome), in which an entire extra copy of chromosome 18 is present, and from 18p deletion syndrome, in which part of the short arm (18p) is lost — the causes and severity of symptoms differ for each. Because the names are similar, they are easily confused, so care is needed.

Condition	Chromosomal Change	Characteristics
Trisomy 18 (Edwards syndrome)	Three copies of chromosome 18 (one entire extra copy)	Often accompanied by severe complications affecting multiple organs, including the heart and kidneys
18p deletion syndrome	Partial deletion of the short arm (p) of chromosome 18	Mainly short stature and mild-to-moderate intellectual disability
18q deletion syndrome	Partial deletion of the long arm (q) of chromosome 18 (18q21→qter)	Diverse symptoms including developmental delay, hearing loss, and hypomyelination

For a detailed look at how the symptoms differ, please also see our articles explaining trisomy 18 (Edwards syndrome) and 18p deletion syndrome. Checking exactly what chromosomal change is described in your test result — whether it is a trisomy or a deletion, and whether it involves the long arm or the short arm — is the first step toward understanding it correctly.

Treatment and Prognosis | Symptomatic Care and the Long-Term Outlook

There is no treatment that cures 18q deletion syndrome at its root; care combines symptom-based treatments to support quality of life. Involvement of a team spanning multiple specialties is standard practice.

• Developmental support: Speech therapy, physical therapy, and occupational therapy help support development.
• Endocrine management: Hormonal abnormalities are managed with treatments such as growth hormone replacement therapy.
• Hearing support: Hearing aids and ENT rehabilitation tailored to the condition of the ear canal are provided.
• Comprehensive medical management: Multiple specialties — pediatrics, endocrinology, otolaryngology, neurology, and others — coordinate care.

Prognosis varies depending on symptom severity and whether appropriate medical support is available. That said, an early diagnosis followed by developmental support, endocrine management, and related care can meaningfully improve quality of life. Absent complications such as congenital heart disease or severe infections, the long-term survival outlook is considered relatively good.

17p12 Deletion Syndrome (Charcot-Marie-Tooth Disease Type 1A)

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Status as a Designated Intractable Disease and Pediatric Chronic Specific Disease

18q deletion syndrome is positioned as one of the 11 conditions that make up Designated Intractable Disease 139, “Congenital Hypomyelinating Leukoencephalopathy.” When a child is affected, subsidy programs for pediatric chronic specific diseases are also worth considering.

Both the designated intractable disease and pediatric chronic specific disease programs can provide medical expense assistance to those who meet certain severity criteria. The most reliable way to confirm eligibility and procedures is through your local municipal office or treating physician. Intractable Disease Consultation and Support Centers can also advise on how to use these programs.

Emotional and Financial Burden on Parents, and Available Support

Because long-term therapy and medical management are needed, parents can face significant financial and emotional burdens. Precisely because this is such a rare condition, building an environment where families don’t feel isolated becomes an important source of support.

What I’ve come to feel through my own clinical practice is that, precisely because information on this condition is so limited, keeping families from becoming isolated matters more than anything else. Connecting with other families who have had similar experiences, and knowing about public consultation resources early on, both become sources of strength for the long road of therapy and support ahead.

When you want to look up information on intractable or rare diseases, the Japan Intractable Diseases Information Center is a good starting point. For developmental support, the National Rehabilitation Center for Persons with Disabilities’ Developmental Disorders Information and Support Center summarizes consultation resources and approaches to support. And if you’d like to deepen your understanding of prenatal testing itself from a neutral standpoint, information from the Japanese Association of Medical Sciences’ Committee for the Certification System for Prenatal Testing can also be a helpful reference.

Closer to home, local public health centers, child development support centers, and family support groups made up of people with similar experiences can all serve as sources of support. Since subsidy programs for medical expenses and therapy are also available, please check with your local municipal office.

Frequently Asked Questions

Q. Can NIPT detect 18q deletion syndrome?

It is not covered by basic NIPT (trisomy 13, 18, and 21) or the basic 23-condition microdeletion panel. It is included as a target condition in the expanded 116-condition panel based on whole-genome analysis, but because NIPT is a non-definitive screening test, a positive result alone does not confirm the diagnosis. A definitive diagnosis requires chromosome analysis by amniocentesis (G-banding and FISH).

Q. Is this the same as trisomy 18 (Edwards syndrome)?

No, they are different conditions. Trisomy 18 involves an entire extra copy of chromosome 18 and is often accompanied by severe complications affecting multiple organs. 18q deletion syndrome involves the loss of part of the long arm (q) of chromosome 18, and its causes and symptom severity differ. Please check what is specifically stated in your test result to tell them apart.

Q. How is the diagnosis confirmed?

Diagnosis is made by combining clinical symptoms such as growth failure and developmental delay, abnormal white matter findings on MRI, and confirmation of the 18q21→qter deletion through G-banding chromosome analysis and FISH. Prenatally, this can be examined via amniocentesis or chorionic villus sampling; after birth, it can be examined via a blood test.

Q. Is it certified as a designated intractable disease?

18q deletion syndrome is positioned as one of the 11 conditions that make up Designated Intractable Disease 139, “Congenital Hypomyelinating Leukoencephalopathy.” For children, it may also qualify for pediatric chronic specific disease assistance. Since certification depends on severity criteria, please confirm with your treating physician or your local municipal office.

Q. Was this caused by something in the mother’s lifestyle during pregnancy?

No, it was not. Most cases arise from a spontaneous, sporadic new mutation (de novo). In rare cases, one parent carries a balanced translocation, but even then, lifestyle habits are not the cause. If you have concerns, please consult a specialist through genetic counseling.

Q. How severe are the symptoms?

Symptom severity varies greatly from person to person. Whether the deleted region includes the MBP gene, the TCF4 gene, or both also affects how symptoms present. Rather than applying an average picture, it’s important to carefully observe the child in front of you and build the support they need from there.