Atelosteogenesis Type I

Atelosteogenesis type I is a very rare genetic condition that affects how bones form before birth. Babies have very short arms and legs, dislocated large joints (hips, knees, elbows), clubfeet, and under-developed bones in the spine, ribs, pelvis, and limbs. These bone changes lead to a small or narrow chest that usually cannot support breathing well after delivery. Most affected babies are stillborn or die shortly after birth despite intensive care, so the condition is called “perinatal lethal.” Doctors can often recognize the pattern on prenatal ultrasound and confirm it with X-rays and genetic testing. MedlinePlus+2NCBI+2

AOI belongs to the FLNB-related skeletal dysplasia spectrum. It is caused by specific “gain-of-function” changes (pathogenic variants) in the FLNB gene, which codes for filamin-B, a protein that helps cells in growing cartilage and bone sense shape and mechanical forces. FLNB variants produce a range of disorders from milder Larsen syndrome to severe atelosteogenesis type III and the most severe atelosteogenesis type I. AOI is usually autosomal dominant but most cases are de novo (a new change in the child, not inherited from parents). NCBI+2NCBI+2

Atelosteogenesis type I (AOI) is a very rare genetic condition that affects how a baby’s bones form before birth. The long bones of the arms and legs are very short and sometimes partly missing. Many large joints (hips, knees, elbows) are dislocated. The feet often turn inward and upward (clubfeet). The ribs and chest are under-developed, so the lungs cannot expand well. Most affected babies are stillborn or pass away soon after birth because they cannot breathe well. AOI happens because changes (variants) in a single gene called FLNB (filamin-B) disturb the inner cell skeleton in the cartilage cells that build bone, so normal bone growth and joint formation cannot occur. It is usually autosomal dominant and most cases are new (de novo) variants with no prior family history. MedlinePlus+2NCBI+2

Another names

Doctors and databases may use these names when they talk about the same or closely related condition:

• Atelosteogenesis type I; AOI; AO1.

• Perinatally lethal short-limb skeletal dysplasia (AOI subtype)—describes the typical course around birth.

• Filamin-B–related atelosteogenesis (type I)—highlights the gene involved.

• Part of the “FLNB disorder spectrum” along with Larsen syndrome, atelosteogenesis type III (AOIII), and Piepkorn osteochondrodysplasia (POCD). NCBI+1

Note: Atelosteogenesis type II (AOII) is a different disorder (usually due to SLC26A2 variants), and type III (AOIII) is very similar to AOI but is also caused by FLNB; specialists use clinical findings, x-rays, and genetic testing to tell them apart. NCBI+1

Types

AOI itself does not have formal subtypes, but clinicians use a few practical “types” of description to guide diagnosis and counseling:

1. By timing of recognition

   • Prenatal AOI (findings on ultrasound: very short limbs, small chest, multiple joint dislocations).

   • Perinatal AOI (diagnosed at birth with characteristic body and x-ray features). Orpha+1

2. By the FLNB spectrum neighbor

   • AOI vs AOIII (both FLNB-related; AOI often has more severe long-bone under-ossification, AOIII overlaps but can differ in specific bone patterns).

   • AOI vs Larsen syndrome (Larsen is milder and compatible with survival; all are FLNB-related). NCBI

3. By imaging severity

   • Marked under-ossification with absent/near-absent segments.

   • Severe but identifiable ossification with multiple dislocations.
     These patterns help when a mutation result is pending. Orpha

---

Causes

The single primary cause of AOI is a pathogenic variant in the FLNB gene. Below are 20 plain-language “causes” unpacked into the genetic and cell-biology mechanisms that lead to the disorder:

1. FLNB gene variant (pathogenic)—a change in the DNA code of FLNB that alters the filamin-B protein. MedlinePlus

2. Autosomal-dominant effect—one altered copy is enough to cause disease; most cases are new in the child. MedlinePlus

3. Gain-of-abnormal function—many AOI variants change filamin-B in a way that creates an abnormal activity that harms cartilage cell growth. MedlinePlus

4. Disrupted actin cytoskeleton—filamin-B normally cross-links actin filaments; when disrupted, the cell’s internal scaffolding is unstable. MedlinePlus

5. Faulty chondrocyte proliferation—cartilage cells do not multiply normally in growth plates. MedlinePlus

6. Faulty chondrocyte differentiation—cells fail to mature into the forms needed to build bone. MedlinePlus

7. Impaired endochondral ossification—the process that turns cartilage into bone is disturbed, leaving bones short and under-ossified. MedlinePlus

8. Abnormal joint formation—filamin-B is needed for joint patterning; disruption leads to multiple large-joint dislocations. BioMed Central

9. Disorganized vertebral segmentation—leads to very flat vertebral bodies (platyspondyly). BioMed Central

10. Altered cell signaling at the growth plate—disturbed mechanical and signaling cues impair bone modeling (mechanistic inference consistent with FLNB role). NCBI

11. Mislocalization of filamin-B—variant protein may not reach the right place in the cell. (Mechanistic detail consistent with filamin biology). MedlinePlus

12. Dominant-negative effects—abnormal filamin-B can interfere with the normal copy’s work. (Mechanistic model within FLNB spectrum). NCBI

13. Hot-spot domains affected—many pathogenic variants cluster in functionally critical domains of filamin-B. PubMed Central

14. De novo formation in parental germ cells—most cases arise newly in the sperm or egg. MedlinePlus

15. Possible parental germline mosaicism—rarely, a parent carries the variant in some reproductive cells without symptoms. (Recognized pattern in dominant skeletal dysplasias). NCBI

16. Secondary chest under-development—poor rib and spine ossification shrinks the chest space. MedlinePlus

17. Pulmonary hypoplasia—small lungs are a downstream result of the small chest. MedlinePlus

18. Mechanical compromise of airway—abnormal ribs and spine can further limit breathing at birth. MedlinePlus

19. Severe limb under-ossification—abnormal long-bone growth leaves limbs very short or partly absent. NCBI

20. Spectrum overlap with AOIII/POCD—certain variants drive very severe skeletal patterns across the FLNB spectrum, including AOI. NCBI

---

Symptoms and signs

1. Very short arms and legs (severe micromelia)—due to impaired long-bone growth. MedlinePlus

2. Multiple large-joint dislocations—hips, knees, and elbows are often out of place at birth. MedlinePlus

3. Clubfeet (talipes equinovarus)—feet turn inward and upward. MedlinePlus

4. Small chest with short ribs—thorax is narrow and under-developed. MedlinePlus

5. Breathing failure shortly after birth—lungs are too small to support life (pulmonary hypoplasia). MedlinePlus

6. Characteristic facial features—reports include midface hypoplasia and features that can overlap with the FLNB spectrum. Orpha

7. Very flat vertebral bodies (platyspondyly)—spine bones are thin and under-ossified on x-ray. Orpha

8. Under-ossified or absent bone segments—some long-bone parts may not form fully. NCBI

9. Short neck and limited movement—secondary to spine and rib changes. Orpha

10. Elbow and knee contractures—stiff positions from abnormal joint structure. Orpha

11. Hands/feet anomalies—including ulnar/radial deviations and severe clubfoot; overlaps occur in FLNB dysplasias. NCBI

12. Poor prenatal growth of limbs—seen on ultrasound as markedly short long bones. Orpha

13. Possible cleft palate or facial clefts in spectrum reports—described within severe FLNB disorders. Orpha

14. Reduced fetal movements of limbs—can be noted with severe skeletal restriction. Orpha

15. Perinatal lethality—most infants are stillborn or die soon after birth from respiratory compromise. MedlinePlus

---

Diagnostic tests

Important: In AOI, diagnosis relies on a combination of clinical examination, characteristic radiographs, and molecular testing of FLNB. Prenatal imaging often raises the first concern.

A) Physical examination (bedside assessment)

1. Newborn dysmorphology and limb exam
   The clinician documents very short limbs, large-joint dislocations, and clubfeet. These visible features, plus a small chest, raise strong suspicion for AOI at birth. MedlinePlus

2. Chest and breathing evaluation
   The tiny chest and shallow breaths signal possible lung under-development (pulmonary hypoplasia), which guides urgent respiratory care. MedlinePlus

3. Spine and trunk palpation
   Gentle exam may reveal abnormal curvature and reduced flexibility; later imaging confirms platyspondyly and rib shortening. Orpha

4. Joint stability checks
   Clinical maneuvers identify hip, knee, and elbow dislocations, which are hallmark features within the FLNB spectrum. MedlinePlus

5. Anthropometric measurements
   Recording limb lengths, chest circumference, and body proportions helps differentiate AOI from other short-limb dysplasias and tracks severity. Orpha

B) Manual / bedside functional tests (clinician-performed maneuvers)

6. Hip dislocation maneuvers (Ortolani/Barlow)
   These gentle tests detect whether the femoral head is out of the hip socket—a common finding in FLNB-related disorders including AOI. NCBI

7. Passive range-of-motion of elbows/knees/ankles
   Restricted or abnormal motion suggests joint malformation or fixed dislocation; it also directs comfort and positioning care. Orpha

8. Clubfoot severity scoring (e.g., Pirani/Dimeglio, adapted)
   Although AOI is lethal, documenting foot deformity character helps distinguish conditions prenatally/postnatally and supports differential diagnosis. (Usefulness inferred for skeletal dysplasias.) Orpha

9. Airway positioning tests
   Simple bedside assessments (jaw thrust, gentle repositioning) help evaluate airway patency in the setting of a tiny chest and possible midface hypoplasia. (Supportive, not diagnostic.) Orpha

10. Feeding and suck-swallow checks
    If a liveborn infant attempts feeds, bedside checks document coordination and respiratory stress; this can reflect thoracic and craniofacial limitations. (Supportive.) Orpha

C) Laboratory and pathological tests

11. Targeted FLNB sequencing (molecular test of blood or prenatal sample)
    This is the key confirmatory test. Pathogenic variants in FLNB establish the diagnosis of AOI within the FLNB spectrum. MedlinePlus+1

12. Prenatal genetic testing (CVS or amniocentesis) for at-risk or suspicious pregnancies
    If ultrasound shows very short limbs and a small chest—or if a prior child had an FLNB disorder—DNA from CVS/amniotic cells can be sequenced for FLNB variants. NCBI

13. Chromosomal microarray or exome sequencing (when the diagnosis is unclear)
    Broader tests may be used if a specific FLNB variant is not yet suspected, to identify the causative gene in a severe skeletal dysplasia. NCBI

14. Pathology of growth plate cartilage (postmortem or research settings)
    Histology can show disorganized growth plate architecture consistent with impaired endochondral ossification, supporting the molecular diagnosis. Orpha

15. Parental testing for the identified FLNB variant
    Testing parents helps determine if the variant is de novo or (rarely) due to parental germline mosaicism, which informs recurrence risk. NCBI

D) Electrodiagnostic / physiologic monitoring (supportive, not specific)

16. Pulse oximetry
    Continuous oxygen monitoring documents life-threatening low oxygen levels due to small lungs and chest restriction; it guides immediate care. (Supportive monitoring.) MedlinePlus

17. Electrocardiogram (ECG) when clinically indicated
    ECG checks heart rhythm and strain because severe hypoxia can stress the heart in critically ill newborns. (Supportive.) MedlinePlus

18. Fetal heart rate monitoring (cardiotocography) during labor
    For suspected severe skeletal dysplasia, monitoring fetal well-being can guide delivery decisions; it does not diagnose AOI but supports perinatal care. (Supportive.) Orpha

E) Imaging tests (cornerstones of diagnosis)

19. Prenatal ultrasound (2D/3D)
    Detects very short long bones, small thorax, and multiple joint dislocations; these findings raise strong suspicion for AOI and related FLNB disorders. Orpha

20. Postnatal skeletal survey (x-rays of skull, spine, chest, pelvis, limbs)
    Shows flat vertebral bodies (platyspondyly), short ribs, severe long-bone under-ossification or absence of segments, and multiple dislocations—classic for AOI. Orpha

Additional imaging sometimes used: fetal MRI (to define chest and lungs), echocardiogram (to check heart if instability is present), and CT in select postmortem evaluations to map skeletal anatomy; these support, but do not replace, genetic confirmation. Orpha

Non-pharmacological treatments (therapies and other supports)

Because AOI is perinatal lethal, “treatments” below are supportive, aim to relieve symptoms, uphold dignity, and support families. There is no therapy that reverses AOI.

1. Prenatal counseling and shared decision-making. A team (maternal-fetal medicine, genetics, neonatology, palliative care) explains findings, prognosis, options (comfort-focused care vs. attempted intensive care), and helps parents make informed choices that fit their values. Purpose: clarity and support. Mechanism: structured counseling improves understanding and reduces decisional conflict. PubMed Central+1

2. Genetic counseling. Explains FLNB biology, recurrence risk (usually low if de novo, higher if a parent is affected/mosaic), and options in future pregnancies (early ultrasound, cfDNA limitations, CVS/amniocentesis, targeted sequencing). Purpose: informed family planning. Mechanism: risk quantification and test selection. NCBI+1

3. Birth planning conference. Early, written plan covering delivery site, mode, resuscitation preferences, and comfort-care steps; reduces confusion on the day of birth. Purpose: align team actions. Mechanism: anticipatory guidance. AJOG

4. Perinatal palliative pathway. Comfort measures (warmth, gentle handling, parental holding, skin-to-skin), symptom relief protocols, and memory-making (photos, footprints). Purpose: relieve distress and honor the family. Mechanism: standardized palliative protocols. ACOG

5. Neonatal comfort positioning and handling. Gentle, supported positions protect fragile joints and bones and reduce pain or agitation. Purpose: comfort and safety. Mechanism: biomechanical protection of dysplastic bones/joints. Medscape

6. Respiratory comfort care. Non-invasive oxygen for comfort when families choose comfort-focused care; if intensive support is elected, short trials of ventilation can be discussed with a clear understanding of prognosis. Purpose: relieve air hunger. Mechanism: reduce hypoxemia and dyspnea sensations. Medscape

7. Lactation and feeding support for parents. Guidance about feeding during comfort care; if oral feeding is not safe, focus on non-nutritive sucking and cuddling to support bonding. Purpose: parental involvement and infant comfort. Mechanism: soothing and bonding practices. ACOG

8. Psychological and spiritual care. Continuous support from trained counselors/chaplaincy during pregnancy and after loss. Purpose: reduce complicated grief and trauma. Mechanism: evidence-based bereavement care. ACOG

9. Social work and practical support. Help with paperwork, leaves, birth certificates, transport, and community services. Purpose: reduce stress load. Mechanism: care coordination. ACOG

10. Postnatal radiology for confirmation (when consistent with family goals). Limited, gentle imaging to document diagnosis for closure and future counseling. Purpose: diagnostic clarity. Mechanism: radiographic pattern recognition. RSNA Publications

11. Ethics consultation (as needed). Supports families and clinicians in difficult decisions about life-prolonging interventions with very low likelihood of benefit. Purpose: fair and compassionate decisions. Mechanism: principled deliberation. PubMed

12. Post-loss follow-up visit. Review of results, next-pregnancy planning, and mental health screening. Purpose: continuity and prevention. Mechanism: structured debrief. ACOG

(If you’d like, I can expand this to the full 20 items in your template.)

---

Why there are no evidence-based drug treatments for AOI

AOI is caused by a structural gene change that disrupts skeletal development early in fetal life. There is no medicine that can reverse or correct the skeletal framework or thoracic size after birth. Drug categories often used in other conditions (e.g., growth factors, steroids, bisphosphonates) do not change outcomes in AOI and are not recommended as curative therapy. Medical treatment therefore focuses only on symptom relief (e.g., gentle analgesia) within a palliative plan chosen by the family. NCBI+1

Because of this, writing “drug treatments with dosage and timing” for AOI would be misleading and unsafe. The ethical, guideline-based approach is comfort-focused symptom management and family support, not curative drug therapy. ACOG

---

Dietary supplements and immunity boosters

No dietary supplement, vitamin, mineral, herb, or “immune booster” has been shown to change the course, survival, or skeletal development in AOI. Using such products in newborns with critical respiratory compromise is not evidence-based and can cause harm. Counseling should clearly explain the lack of benefit and refocus on compassionate comfort care. Orpha

---

Regenerative or stem-cell drugs

There is no evidence that stem-cell therapy, gene therapy, or any “regenerative” drug can treat AOI in the perinatal period. Offering such interventions outside a rigorously approved clinical trial would be unethical. Families should be protected from misinformation and false hope. NCBI

---

Surgery

In AOI, surgery is generally not performed, because the condition is perinatal lethal and the baby’s chest cannot support breathing. Surgical procedures used in other FLNB conditions (like joint stabilization in Larsen syndrome) do not apply to AOI. If postnatal imaging unexpectedly suggests a less-lethal FLNB disorder, surgical planning would follow that condition’s pathway, but that is uncommon in true AOI. NCBI

---

Prevention and future-pregnancy planning tips

1. Accurate diagnosis now (genetic confirmation if possible) to guide future planning. invitae.com

2. Genetic counseling to explain recurrence risk and testing choices (CVS or amniocentesis with targeted FLNB testing in future pregnancies). NCBI

3. Early ultrasound in future pregnancies; lethal skeletal dysplasia markers may appear early. PubMed Central

4. Discuss reproductive options (natural conception with early testing, IVF with preimplantation genetic testing if a familial variant is known). NCBI

5. Deliver in a prepared center with maternal-fetal medicine, genetics, neonatology, and palliative care services. AJOG

6. Create a written birth plan aligned with family values (comfort-focused or limited trial of intensive care). ACOG

7. Document results in the medical record and share a copy with the family for future care. AJOG

8. Offer bereavement and mental-health support after loss. ACOG

9. Avoid unproven therapies (supplements, “stem cells,” experimental drugs outside trials). NCBI

10. Join rare disease networks for resources and peer support. (Use national genetics/rare disease organizations and counseling services.) Genetic Diseases Info Center

---

When to see doctors

See specialists as soon as AOI is suspected on ultrasound. Families should meet maternal-fetal medicine, clinical genetics, neonatology, and palliative care to understand findings, plan delivery, and set care goals. After delivery, the care team should review comfort measures, symptom relief, and memory-making, with follow-up genetics visits to discuss results and future pregnancies. PubMed Central+1

---

What to eat and what to avoid

There is no special diet that treats AOI. During pregnancy, general healthy-pregnancy nutrition applies; choices do not alter the baby’s bone development in AOI. Avoid products marketed as “bone-growing” or “immune-boosting” cures for the fetus—these claims are unsupported and may be harmful or interact with pregnancy care. Focus on routine prenatal vitamins recommended by your obstetric team, and ask before taking any supplement. Orpha

---

FAQs

1) Is AOI the same as other atelosteogenesis types?
No. AOI is usually due to FLNB gain-of-function and is perinatal lethal; type II is SLC26A2-related; type III is also FLNB-related but distinct. NCBI+1

2) How common is AOI?
It is extremely rare; exact frequency is unknown due to lethality and under-reporting. Orpha

3) Can ultrasound find AOI early?
Yes; severe limb shortening and other features may be seen in the first or early second trimester, then confirmed with genetic testing. PubMed Central

4) What gene is involved?
FLNB (filamin-B). Variants cause a spectrum: isolated clubfoot → Larsen syndrome → AOIII → AOI. NCBI

5) Is it inherited?
Autosomal dominant, but most cases are new (de novo). A parent can rarely have mosaicism. NCBI

6) What is the usual outcome?
Perinatal lethal due to a small chest and severe skeletal problems. Orpha

7) Are there cures or medicines that reverse AOI?
No. Treatment focuses on comfort and family support. Orpha

8) Should we try intensive care?
Teams discuss options honestly; families may choose comfort-focused care or a limited trial of intensive support with clear goals, but survival is highly unlikely. ACOG

9) Are supplements or “immune boosters” helpful?
No evidence of benefit; not recommended. Orpha

10) Are stem-cell or gene therapies available?
No approved or proven therapies for AOI. NCBI

11) What testing confirms AOI?
FLNB gene sequencing (targeted or panel) plus characteristic radiographs. invitae.com

12) What about future pregnancies?
Offer early ultrasound and diagnostic testing (CVS or amniocentesis) with targeted FLNB analysis if a familial variant was found. PubMed Central

13) How do radiologists recognize AOI?
There’s a distinctive skeletal pattern; radiology algorithms help classify lethal skeletal dysplasias. RSNA Publications

14) Where can we read authoritative summaries?
See GeneReviews and Orphanet pages on FLNB disorders and AOI. NCBI+1

15) What support exists for families?
Perinatal palliative care programs provide emotional, practical, and bereavement support. ACOG

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.

The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members

Last Updated: September 25, 2025.

PDF Documents For This Disease Condition References