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PubMed This is a summary of 16 peer-reviewed journal articles Updated
Genetics

What is contiguous gene syndrome in X-linked Ichthyosis?

At a Glance

A contiguous gene syndrome in Recessive X-linked Ichthyosis happens when the genetic deletion causing the condition is large enough to erase neighboring genes. This can lead to additional health issues like short stature, delayed puberty, or neurodevelopmental differences alongside skin scaling.

In this answer

2 sections

01

How a Large Deletion Affects the Body

02

Mapping the Deletion with CMA

When a boy is diagnosed with Recessive X-linked Ichthyosis (RXLI), it is typically because a specific gene called the STS gene is missing or altered on his X chromosome [1]. Because RXLI is an X-linked condition, these genetic changes almost exclusively affect boys [1]. Chromosomes are packed tightly with thousands of genes located right next to each other. A contiguous gene syndrome occurs when the genetic missing piece (deletion) that removes the STS gene is large enough that it also erases one or more of these neighboring genes [1][2]. Because these neighboring genes have their own important functions in the body, losing them can cause additional health conditions beyond the skin scaling seen in RXLI [2].

How a Large Deletion Affects the Body

It is important to remember that many children with RXLI only have a deletion involving the STS gene and do not have a contiguous gene syndrome. The extra symptoms a child might experience depend entirely on exactly which, if any, neighboring genes are included in their specific deletion [3].

The X chromosome has a specific region (known as Xp22.3) where the STS gene is located [1]. If the genetic deletion extends past the boundaries of the STS gene, it can take out adjacent genes [4]. If genetic testing shows a larger deletion, some of the conditions that could be part of an RXLI contiguous gene syndrome include:

  • Kallmann Syndrome: This occurs if the deletion includes a nearby gene called the ANOS1 gene (formerly known as KAL1) [1]. Kallmann syndrome affects hormones and sensory nerves, leading to delayed or absent puberty and anosmia (an inability to smell) [4].
  • Short Stature: If a gene called SHOX is missing, it can affect bone growth [5]. This leads to the child having a much shorter height than expected for their age and family history [6].
  • Skeletal Differences: Deletion of the ARSL gene can cause a rare bone condition called Chondrodysplasia Punctata 1 (CDPX1) [7]. This may present at birth with features like a flattened bridge of the nose, short fingers, or small calcium spots on the ends of bones (stippled epiphyses) [8].
  • Neurodevelopmental Differences: Larger deletions in this specific area of the X chromosome are also associated with an increased chance of neurodevelopmental conditions [9]. These can include attention-deficit hyperactivity disorder (ADHD), behavioral conditions, or sometimes seizures (epilepsy) [10][11]. Keep in mind that these are associated risks with very large deletions, not guarantees.

Mapping the Deletion with CMA

Because knowing exactly which genes are missing is so important for your child’s long-term care, doctors use a specialized genetic test called a Chromosomal Microarray (CMA).

Unlike older genetic tests (like a standard karyotype) that just look at the overall shape of the chromosomes, a CMA zooms in closely on the DNA to find submicroscopic missing pieces [12]. It maps the precise breakpoints of the deletion—showing exactly where the missing genetic section starts and stops [13]. By mapping this deletion, the CMA tells your medical team exactly which genes were lost alongside the STS gene [14].

Having this precise map allows your doctors to know which specific conditions to watch for and treat proactively, rather than waiting for symptoms to appear unexpectedly [15]. If your child’s genetic testing only confirmed the RXLI but didn’t map the full deletion size, a CMA is often recommended as a critical next step to rule out a contiguous gene syndrome [16].

Common questions in this guide

What is a contiguous gene syndrome?
A contiguous gene syndrome occurs when a genetic deletion is large enough to remove not only the primary gene responsible for a condition, but also adjacent genes. In RXLI, this happens when the missing genetic piece on the X chromosome extends beyond the STS gene.
What other health conditions can be caused by a large STS gene deletion?
Depending on which specific neighboring genes are missing, a child could experience delayed puberty, an inability to smell, short stature, or rare bone conditions. It can also increase the chance of neurodevelopmental conditions like ADHD or seizures.
How do doctors find out if my child has a contiguous gene syndrome?
Doctors use a specialized genetic test called a Chromosomal Microarray (CMA). This test maps the exact size of the missing genetic section to determine precisely which genes were lost alongside the STS gene.
Does every boy with RXLI have a contiguous gene syndrome?
Many children with RXLI only have a deletion involving the STS gene and do not develop a contiguous gene syndrome. The presence of additional symptoms depends entirely on whether neighboring genes are included in their specific genetic deletion.
What happens if the ANOS1 gene is deleted along with the STS gene?
The ANOS1 gene is located near the STS gene on the X chromosome. If a large deletion erases both the STS and ANOS1 genes, the child will develop Kallmann syndrome, which affects hormones, delays puberty, and causes an inability to smell.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Did my child's genetic testing (such as a Chromosomal Microarray) map the exact size and breakpoints of their deletion?
  2. 2.Based on the genetic test results, are there any specific neighboring genes missing besides the STS gene?
  3. 3.What early warning signs or physical milestones should we be watching for regarding puberty, growth, or behavior?
  4. 4.Do we need to see any other specialists, such as an endocrinologist or neurologist, based on this genetic map?

Questions For You

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Related questions

Can Females Have Recessive X-Linked Ichthyosis Symptoms?Do Eye Spots in X-Linked Ichthyosis Affect Vision?Does Recessive X-Linked Ichthyosis Improve With Age?How Is Recessive X-Linked Ichthyosis Inherited from Fathers?How Do Teens Cope With Recessive X-Linked Ichthyosis?Is ADHD Related to Recessive X-Linked Ichthyosis?Is Salicylic Acid Safe for Children with RXLI?What Are the Best Bath Additives for RXLI Scales?What Are RXLI Pregnancy Labor Complications?What Are Oral Retinoid Side Effects for RXLI?What Does Low uE3 on a Prenatal Screen Mean for RXLI?RXLI vs. Ichthyosis Vulgaris: What's the Difference?What Is the Risk of Atrial Fibrillation With RXLI?Why Does Recessive X-Linked Ichthyosis Cause Low Vitamin D?

References

References (16)
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    Kallmann syndrome and ichthyosis: a case of contiguous gene deletion syndrome.

    Berges-Raso I, Giménez-Palop O, Gabau E, et al.

    Endocrinology, diabetes & metabolism case reports 2017; (2017()).

    PMID: 30352392
  2. 2

    Novel Microdeletion in the X Chromosome Leads to Kallmann Syndrome, Ichthyosis, Obesity, and Strabismus.

    Ma W, Mao J, Wang X, et al.

    Frontiers in genetics 2020; (11()):596 doi:10.3389/fgene.2020.00596.

    PMID: 32670353
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    ATR-16 syndrome: mechanisms linking monosomy to phenotype.

    Babbs C, Brown J, Horsley SW, et al.

    Journal of medical genetics 2020; (57(6)):414-421 doi:10.1136/jmedgenet-2019-106528.

    PMID: 32005695
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    Kallmann Syndrome and X-linked Ichthyosis Caused by Translocation Between Chromosomes X and Y: A Case Report.

    Sait H, Srivastava P, Dabadghao P, Phadke SR

    Journal of reproduction & infertility 2021; (22(4)):302-306 doi:10.18502/jri.v22i4.7657.

    PMID: 34987993
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    A novel report of a fertile female with partial Y chromosome gain completing a healthy pregnancy.

    Coleman J, Kavanagh K, Kesterton I, et al.

    American journal of medical genetics. Part A 2023; (191(12)):2884-2889 doi:10.1002/ajmg.a.63374.

    PMID: 37638701
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    [Genetic study of a child carrying a maternally derived unbalanced 46,Y,der(X)t(X;Y)(p22;q11) chromosomal translocation].

    Yin T, Wang Y, Wang Z, et al.

    Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 2021; (38(4)):376-379 doi:10.3760/cma.j.cn511374-20200321-00188.

    PMID: 33834470
  7. 7

    A novel frameshift deletion variant of ARSL associated with X-linked recessive chondrodysplasia punctata 1: a case report and literature review of prenatal, confirmed cases.

    Zhou L, Peng Y, Chen J, et al.

    BMC medical genomics 2024; (17(1)):253 doi:10.1186/s12920-024-02029-9.

    PMID: 39425194
  8. 8

    Prenatal findings in a fetus with X-linked recessive type of chondrodysplasia punctata (CDPX1): a case report with novel mutation.

    He G, Yin Y, Zhao J, et al.

    BMC pediatrics 2019; (19(1)):250 doi:10.1186/s12887-019-1629-x.

    PMID: 31337364
  9. 9

    A genetic variant within STS previously associated with inattention in boys with attention deficit hyperactivity disorder is associated with enhanced cognition in healthy adult males.

    Humby T, Fisher A, Allen C, et al.

    Brain and behavior 2017; (7(3)):e00646 doi:10.1002/brb3.646.

    PMID: 28293481
  10. 10

    X-linked ichthyosis associated with psychosis and behavioral abnormalities: a case report.

    Malik A, Amer AB, Salama M, et al.

    Journal of medical case reports 2017; (11(1)):267 doi:10.1186/s13256-017-1420-2.

    PMID: 28934990
  11. 11

    Case report: Sex-specific characteristics of epilepsy phenotypes associated with Xp22.31 deletion: a case report and review.

    Wu Y, Wu D, Lan Y, et al.

    Frontiers in genetics 2023; (14()):1025390 doi:10.3389/fgene.2023.1025390.

    PMID: 37347056
  12. 12

    Comparison of chromosomal microarray and karyotyping in prenatal diagnosis using 491 amniotic fluid samples.

    Yang Y, Jiang X

    Medicine 2024; (103(49)):e40822 doi:10.1097/MD.0000000000040822.

    PMID: 39654217
  13. 13

    Diagnostic Yield of Chromosomal Microarray Analysis in a Cohort of 300 Indian Patients.

    Lall MB, Joshi A, Agarwal S, et al.

    Indian journal of pediatrics 2026; (93(1)):36-47 doi:10.1007/s12098-025-05519-5.

    PMID: 40338472
  14. 14

    Phenotypes of children with 20q13.3 microdeletion affecting KCNQ2 and CHRNA4.

    Okumura A, Atsushi Ishii , Shimojima K, et al.

    Epileptic disorders : international epilepsy journal with videotape 2015; (17(2)):165-71 doi:10.1684/epd.2015.0746.

    PMID: 26030193
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    Chromosomal Microarray Analysis for the Prenatal Diagnosis in Fetuses with Nasal Bone Hypoplasia: A Retrospective Cohort Study.

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    Risk management and healthcare policy 2021; (14()):1533-1540 doi:10.2147/RMHP.S286038.

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

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This page provides educational information about contiguous gene syndromes in RXLI. Always consult a geneticist or pediatrician for interpretations of specific genetic testing results and medical advice for your child.

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