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PubMed This is a summary of 12 peer-reviewed journal articles Updated
Medical Genetics · Kyphoscoliotic Ehlers-Danlos Syndrome

Symptoms, Progression, and Avoiding Misdiagnosis in kEDS-PLOD1

At a Glance

Kyphoscoliotic Ehlers-Danlos syndrome (kEDS-PLOD1) causes early severe muscle weakness, progressive spinal curvature, and hypermobile joints. Early diagnosis is critical to establish monitoring for severe, life-threatening complications like eye fragility and arterial aneurysms.

Navigating the symptoms of Kyphoscoliotic Ehlers-Danlos Syndrome (kEDS-PLOD1) requires an understanding of how collagen fragility affects different systems of the body. While every patient’s experience is unique, certain patterns in musculoskeletal, ocular, and vascular health are characteristic of this condition. You can return to the Home Page for a broader overview.

The Hallmark Symptoms

The three “major” signs of kEDS-PLOD1 often appear early in life, though they can vary in severity even among members of the same family [1][2].

  • Congenital Muscular Hypotonia: This is often the first sign noticed. Infants may appear “floppy,” have poor muscle tone, and experience delays in reaching motor milestones like sitting, crawling, or walking [2][3].
  • Progressive Kyphoscoliosis: This refers to a curve in the spine that is both sideways (scoliosis) and forward-to-back (kyphosis). While it is typically present at birth or within the first year of life, in some cases, the curve may not appear until later in childhood [2][1].
  • Generalized Joint Hypermobility: Joints may be excessively flexible, leading to frequent subluxations (partial dislocations) or full dislocations of the shoulders, hips, and knees [2][3].

Ocular and Vascular Complications

Because collagen is a vital component of the eyes and blood vessels, kEDS-PLOD1 involves risks that require specialized monitoring.

  • Ocular (Eye) Fragility: Patients may have blue sclera (a bluish tint to the whites of the eyes) [4]. More serious risks include brittle cornea (thinning of the eye’s outer layer) and keratoglobus (a bulging, globe-like shape of the cornea) [4][5]. These conditions make the eye more vulnerable to rupture even from minor trauma [4].
  • Vascular (Blood Vessel) Fragility: kEDS-PLOD1 is associated with an increased risk of aneurysms (bulges in blood vessel walls) and spontaneous arterial rupture [6][7]. While more common in adults, these complications have been documented as early as childhood, making regular vascular imaging a cornerstone of care [8][7].

🚨 Emergency “Red Flags”

Because of the risk of vascular rupture, it is critical to know what a severe event feels like. Seek immediate emergency care if you or your child experience:

  • Sudden, severe, or unexplained pain in the chest, abdomen, or back (often described as a “tearing” or “ripping” sensation).
  • Sudden, severe headache (the “worst headache of your life”).
  • Unexplained dizziness, fainting, or sudden vision changes.
    Make sure to present your emergency protocol letter (see Building Your Expert Team) so ER doctors know you are at high risk for vascular events [6].

Adult Risks and Pregnancy

As patients transition into adulthood, the management of joint stability and vigilant monitoring for vascular complications becomes the primary clinical focus [6][7]. Additionally, pregnancy carries severe, potentially life-threatening risks for adults with kEDS-PLOD1 due to the combination of tissue fragility and increased strain on the vascular system [2][6]. Consultation with high-risk maternal-fetal medicine specialists and genetic counselors is strictly required for family planning.

Distinguishing PLOD1 from FKBP14

There are two primary genetic causes of kEDS: mutations in the PLOD1 gene and the FKBP14 gene. While they share many symptoms, there are key differences:

Feature kEDS-PLOD1 kEDS-FKBP14
Hearing Typically normal Sensorineural hearing loss is common [9][10]
Vascular Risk Characteristic and higher risk [6] Recognized but less frequent [9]
Motor Delay Variable May be more prominent/severe [9]

Common Misdiagnoses

Because kEDS-PLOD1 is rare, it is frequently mistaken for other conditions, especially in the early stages:

  • Neuromuscular Disorders: If the spinal curve is not present at birth, severe muscle weakness (hypotonia) may lead doctors to test for muscular dystrophy or other muscle diseases [2].
  • Classical EDS (cEDS): If skin hyperelasticity and joint flexibility are the main features, a patient may be misdiagnosed with the more common classical form of EDS [2].
  • Larsen Syndrome: This condition also features joint dislocations and spinal curves, but it is caused by different genetic mutations [11].

Early diagnosis is critical because it allows for “anticipatory planning”—protecting the eyes and arteries before a major event occurs [12][6].

Common questions in this guide

What are the main signs of kEDS-PLOD1 in infants?
The most common early signs are poor muscle tone, which makes the infant appear unusually floppy and delays motor milestones like sitting and walking. Infants may also be born with or soon develop a complex curve in the spine known as kyphoscoliosis.
What vascular warning signs should kEDS-PLOD1 patients watch for?
Patients should seek immediate emergency care for sudden, severe, tearing pain in the chest, abdomen, or back, or the sudden onset of an extreme headache. Unexplained dizziness, fainting, or vision changes are also critical red flags for a potential blood vessel rupture.
How is kEDS-PLOD1 different from kEDS-FKBP14?
While both conditions cause similar musculoskeletal issues, kEDS-FKBP14 frequently involves hearing loss and more severe motor delays. In contrast, kEDS-PLOD1 patients typically have normal hearing but face a much higher risk of severe vascular complications.
Does kyphoscoliotic EDS affect the eyes?
Yes, the fragile collagen in kEDS-PLOD1 can cause serious eye complications. Patients may have a bluish tint to the whites of their eyes, significant thinning of the cornea, or an abnormally shaped cornea that makes the eye more vulnerable to rupturing from even minor trauma.
Why is kEDS often misdiagnosed early on?
Because the condition is very rare, early symptoms like severe muscle weakness may be mistaken for muscular dystrophy or other neuromuscular disorders. If skin elasticity and loose joints are the main features noticed, patients might be incorrectly diagnosed with the classical form of EDS.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Since there is no congenital scoliosis yet, what specific symptoms should we watch for as growth continues?
  2. 2.Does the absence of hearing loss confirm it is PLOD1 rather than FKBP14, or do we still need genetic testing?
  3. 3.What are the specific warning signs of a vascular event that I should look for?
  4. 4.How can we safely engage in physical activity while protecting the eyes and joints?
  5. 5.What are the specific risks regarding pregnancy, and who should I consult for family planning?

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 (12)
  1. 1

    Rare Cases of PLOD1-Related Kyphoscoliotic Ehlers-Danlos Syndrome in a Korean Family Identified by Next Generation Sequencing.

    Shin YL, Park YN, Jang MA

    Journal of Korean medical science 2020; (35(10)):e96 doi:10.3346/jkms.2020.35.e96.

    PMID: 32174067
  2. 2

    Ehlers Danlos syndrome, kyphoscoliotic type due to Lysyl Hydroxylase 1 deficiency in two children without congenital or early onset kyphoscoliosis.

    van Dijk FS, Mancini GMS, Maugeri A, Cobben JM

    European journal of medical genetics 2017; (60(10)):536-540 doi:10.1016/j.ejmg.2017.07.011.

    PMID: 28757364
  3. 3

    The first case report of Kyphoscoliotic Ehlers-Danlos syndrome of chinese origin with a novel PLOD1 gene mutation.

    Ni X, Jin C, Jiang Y, et al.

    BMC medical genetics 2020; (21(1)):214 doi:10.1186/s12881-020-01154-3.

    PMID: 33129265
  4. 4

    Cataract surgery complications in a patient with brittle cornea syndrome and Ehlers-Danlos syndrome type six: A case report.

    Maurino V, Aiello F, Matarazzo F

    American journal of ophthalmology case reports 2024; (36()):102120 doi:10.1016/j.ajoc.2024.102120.

    PMID: 39139206
  5. 5

    Successful repair of a spontaneous scleral rupture in a patient with type VI Ehlers-Danlos syndrome.

    Lozada R, Amaral C, Alvarez-Falcón S, et al.

    American journal of ophthalmology case reports 2020; (20()):100961 doi:10.1016/j.ajoc.2020.100961.

    PMID: 33102932
  6. 6

    A severe case of PLOD1-related kyphoscoliotic Ehlers-Danlos syndrome associated with several arterial and venous complications: A case report.

    Foy M, Métay C, Frank M, et al.

    Clinical case reports 2023; (11(2)):e6760 doi:10.1002/ccr3.6760.

    PMID: 36860721
  7. 7

    Stroke in Ehlers-Danlos Syndrome Kyphoscoliotic Type: Dissection or Vasculitis?

    Quade A, Wiesmann M, Weis J, et al.

    Pediatric neurology 2017; (74()):92-96 doi:10.1016/j.pediatrneurol.2017.05.017.

    PMID: 28739362
  8. 8

    'Pediatric Ehlers-Danlos syndrome VI with retroperitoneal Hemorrhage: case report and management strategy'.

    Yunus A, Khan M, Jamali AA, Kazi G

    Oxford medical case reports 2025; (2025(7)):omaf119 doi:10.1093/omcr/omaf119.

    PMID: 40718530
  9. 9

    A cohort of 17 patients with kyphoscoliotic Ehlers-Danlos syndrome caused by biallelic mutations in FKBP14: expansion of the clinical and mutational spectrum and description of the natural history.

    Giunta C, Baumann M, Fauth C, et al.

    Genetics in medicine : official journal of the American College of Medical Genetics 2018; (20(1)):42-54 doi:10.1038/gim.2017.70.

    PMID: 28617417
  10. 10

    FKBP14 kyphoscoliotic Ehlers-Danlos Syndrome in adolescent patient: the first Colombian report.

    Ruiz-Botero F, Ramírez-Montaño D, Pachajoa H

    Archivos argentinos de pediatria 2019; (117(3)):e274-e278 doi:10.5546/aap.2019.eng.e274.

    PMID: 31063316
  11. 11

    FKBP14 kyphoscoliotic Ehlers-Danlos syndrome misdiagnosed as Larsen syndrome: a case report.

    Wiegand A, Kastury R, Neogi A, et al.

    Cold Spring Harbor molecular case studies 2023; (9(3)) doi:10.1101/mcs.a006281.

    PMID: 37433679
  12. 12

    Obstetrics and gynecology in Ehlers-Danlos syndrome: A brief review and update.

    Blagowidow N

    American journal of medical genetics. Part C, Seminars in medical genetics 2021; (187(4)):593-598 doi:10.1002/ajmg.c.31945.

    PMID: 34773390

This page provides educational information on kEDS-PLOD1 symptoms and emergency risks. Always consult your medical genetics team or healthcare provider for diagnosis, vascular monitoring, and personalized family planning.

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