Atelosteogenesis type II is a very rare, very severe bone and cartilage growth disorder that begins before birth. It happens because the baby’s cartilage—the soft framework that later turns into bone—does not form and harden in the normal way. As a result, the long bones of the arms and legs are extremely short and partly unossified (not fully turned into hard bone). The chest is small and narrow, the lungs are under-developed, and the airway can be soft and collapsible. Babies usually have a normal-sized head, a cleft palate (an opening in the roof of the mouth), “hitchhiker” thumbs (thumbs that bend outward and backward), clubfeet, and distinctive facial features such as a flat midface and a small lower jaw. Because the chest is small and the lungs are small, most babies sadly die before or shortly after birth due to breathing failure. AO2 belongs to a single gene family of conditions caused by changes in one gene called SLC26A2; this gene provides instructions for a sulfate transporter needed to “sulfate” cartilage molecules so they can build strong cartilage and bone. When the transporter does not work well, cartilage is weak, growth plates are disorganized, and bone formation is seriously disturbed. AO2 is inherited in an autosomal-recessive pattern: both parents are healthy carriers, and the baby receives a non-working copy from each parent. NCBI+2MedlinePlus+2
AO2 is a very severe, inherited condition where cartilage cannot develop normally into bone. Babies have very short arms and legs, a narrow chest, a soft palate opening (cleft palate), thumbs that bend outward (“hitchhiker thumbs”), and clubfeet. Because the chest is small, the lungs cannot grow well (pulmonary hypoplasia), which usually leads to respiratory failure around birth. The condition results from harmful changes in SLC26A2, a gene that helps cartilage cells import sulfate; without enough sulfate, cartilage building blocks (proteoglycans) are undersulfated and the skeleton cannot ossify properly. MedlinePlus+2MedlinePlus+2
Another names
AO2 (short form)
Atelosteogenesis, type II (de la Chapelle type)
De la Chapelle dysplasia (historic name found in early case reports)
SLC26A2-related atelosteogenesis (name highlighting the gene)
Diastrophic dysplasia sulfate transporter–related lethal skeletal dysplasia (descriptive family name) PubMed+2Europe PMC+2
Types
Doctors use “types” in two ways:
Between-disorder types inside the same gene family
The SLC26A2 gene can cause a spectrum of skeletal dysplasias—from lethal to milder forms. These include Atelosteogenesis type II, Achondrogenesis type IB (also lethal), Diastrophic dysplasia (severe but usually compatible with survival), and Recessive multiple epiphyseal dysplasia (milder). AO2 is one of the lethal ends of this spectrum. NCBI+2NCBI+2Clinical sub-groupings used during diagnosis
Within AO2 itself, clinicians sometimes describe prenatal AO2 (detected on ultrasound because of very short limbs and narrow chest), and perinatal AO2 (recognized at delivery), to guide care and counseling. These are not genetic subtypes; they simply mark when the condition is recognized and how severe the breathing compromise looks. (This usage reflects clinical practice described across reviews of SLC26A2 disorders.) NCBI
Causes
Changes (mutations) in the SLC26A2 gene
This gene encodes a sulfate transporter. Disease-causing variants stop the transporter from working properly. Without sulfate transport, cartilage molecules are undersulfated and cannot make strong cartilage. MedlinePlusAutosomal-recessive inheritance
The baby inherits one non-working copy from each parent (both are carriers). When both parents are carriers, each pregnancy has a 25% chance to be affected. MedlinePlusMissense variants
A single amino-acid change can reduce transporter function severely enough to cause AO2, especially when paired with another severe variant. BioMed CentralNonsense or frameshift variants
These can truncate the transporter protein and abolish its function, producing a very severe phenotype like AO2. BioMed CentralSplice-site variants
Changes that disrupt normal splicing can lead to little or no functional transporter. BioMed CentralCompound heterozygosity
Many babies have two different pathogenic variants (one from each parent) that together cause severe transporter failure. NCBIUndersulfation of proteoglycans
Cartilage needs sulfate groups on proteoglycans to stay strong. If sulfation is poor, cartilage is weak and growth plates fail. NCBIDisorganized growth plates
The columns of growing cartilage cells in the long bones do not line up normally, so the bones remain short and partly unossified. NCBIFailed endochondral ossification
The process that converts cartilage to bone is deeply disturbed, leaving patchy, incomplete bone formation. NCBISmall, narrow chest
Because the ribs and chest wall are small, the lungs cannot expand well and lung development is limited. OrphaPulmonary hypoplasia
Under-developed lungs are a direct cause of severe breathing failure at birth. NCBITracheobronchomalacia
The airway can be soft and collapsible, adding to breathing problems in the newborn period. NCBICleft palate formation problems
Abnormal development of palatal shelves leads to a cleft palate, which is common in AO2. OrphaJoint instability and dislocations
Weak connective tissues and malformed joints cause multiple dislocations (knees, hips, elbows), worsening limb function. OrphaClubfeet and hitchhiker thumbs
Distinctive hand-foot anomalies are a hallmark of this gene family and are very frequent in AO2. OrphaCarrier frequency in families or communities
Where carriers are more common, two carriers may more often meet, increasing risk in that population. (This is a general principle in autosomal-recessive disorders; specific AO2 founder effects exist across the SLC26A2 spectrum.) BioMed CentralConsanguinity
Parents who are related have a higher chance of carrying the same rare variant, increasing the risk for autosomal-recessive diseases like AO2. (General recessive-inheritance principle discussed across genetic reviews.) NCBISevere genotype–phenotype combination
Some variant pairs produce especially low transporter activity, pushing the phenotype to the lethal AO2 end of the spectrum. BioMed CentralFailure of prenatal skeletal mineralization
Because cartilage scaffolding is weak, mineral deposition is patchy and delayed, yielding very short limbs on fetal ultrasound. OrphaIneffective repair in utero
The fetus cannot “compensate” for the sulfate transport defect; damage accumulates across the skeleton, causing the full AO2 picture at birth. (Integrates mechanisms summarized in gene-based reviews.) NCBI
Symptoms and Signs
Very short arms and legs (severe micromelia)
The limbs are extremely short because the long bones never develop to normal length. This can be seen before birth and is striking at delivery. OrphaSmall, narrow chest
The ribcage is short and tight, leaving little room for the lungs to expand. This is the key reason for life-threatening breathing problems. OrphaBreathing failure at or soon after birth
Under-developed lungs and a soft airway cause severe respiratory distress; this is unfortunately the most common cause of death. NCBICleft palate
An opening in the roof of the mouth is frequent, adding feeding difficulty to the already serious breathing issues. OrphaHitchhiker thumbs
Thumbs that point outward and backward are a classic visible clue linking AO2 to the SLC26A2 family of disorders. OrphaClubfeet
Feet are turned in and down; the deformity is present at birth and reflects abnormal joint and bone formation. OrphaMultiple joint dislocations
Hips, knees, and sometimes elbows can be dislocated at birth, reflecting joint malformation and tissue laxity. OrphaNormal-sized skull
Unlike some other lethal bone disorders, the skull size is often relatively preserved in AO2, which helps clinicians narrow the diagnosis. OrphaDistinctive facial features
A flat midface and a small lower jaw are commonly described and support the clinical diagnosis. OrphaProtuberant abdomen
Because the chest is small and the abdominal wall is relatively more prominent, the belly can look protuberant. MalaCardsShort neck and limited neck movement
Abnormal spine and rib development can make the neck appear short and stiff.Soft airway (tracheobronchomalacia)
The windpipe and main bronchi can collapse during breathing, making ventilation even more difficult. NCBIPoor weight gain and feeding difficulty (if survival past birth)
A cleft palate and breathing problems make feeding very hard; in rare survivors, growth is extremely poor.Decreased fetal movement (sometimes)
Because limbs are very short and joints are unstable, some families note reduced kicks during pregnancy.Edematous or “puffy” hands and feet in the broader SLC26A2 family
This sign is classic for diastrophic dysplasia; when seen with AO2-like features, it supports involvement of the same gene family. NCBI
Diagnostic Tests
A) Physical Examination
General newborn exam
The doctor looks for extremely short limbs, narrow chest, and typical facial features. These visible clues point strongly to AO2 among lethal skeletal dysplasias. OrphaCleft palate check (oral exam)
Inspecting the palate confirms an opening, which is common and clinically important for feeding and airway protection. OrphaJoint stability exam
Gentle examination shows dislocations of hips, knees, or elbows and the classic hitchhiker thumb position, supporting the diagnosis. OrphaChest size and breathing effort
Measuring and observing chest movement helps gauge how small the ribcage is and how severe the breathing compromise will be. OrphaFoot and hand deformity assessment
Recognizing clubfoot and hand deformities (ulnar deviation, thumb position) narrows the differential towards SLC26A2-related disorders. MalaCards
B) Manual Tests (bedside maneuvers)
Barlow–Ortolani hip maneuvers
Very gentle maneuvers can show hip instability or dislocation, a frequent finding in AO2; these are done carefully to avoid injury.Passive range-of-motion testing
Moving joints through their arcs shows stiffness, instability, or dislocation patterns that match AO2.Airway patency maneuvers during resuscitation
Skilled teams assess how easily the airway can be kept open; difficulty suggests airway softness (tracheobronchomalacia) and a very small chest (functional assessment aligning with clinical and genetic diagnosis). NCBI
C) Laboratory & Pathological Tests
Targeted genetic testing of the SLC26A2 gene
Sequencing looks for two disease-causing variants (one from each parent). Finding biallelic pathogenic variants confirms the diagnosis. NCBIPrenatal molecular testing (CVS or amniocentesis) when variants are known in the family
When a previous child was affected or carriers are known, fetal DNA can be tested to see if the fetus inherited both non-working copies. NCBIMultigene skeletal-dysplasia panels
When ultrasound shows severe short limbs but the exact condition is unclear, broad next-generation sequencing panels that include SLC26A2 help make a definitive diagnosis. BlueShieldCA+1Parental carrier testing
Testing both parents helps confirm recessive inheritance and informs recurrence risk for future pregnancies. MedlinePlus(Specialized) Proteoglycan sulfation studies in fibroblasts (research/rare clinical labs)
Some centers can test sulfation of proteoglycans; reduced sulfation supports the biological mechanism in SLC26A2 disorders. NCBIPathology of cartilage (if performed)
Histology may show poorly organized growth plates and abnormal cartilage matrix, consistent with defective sulfation. PubMed
D) Electrodiagnostic Tests
Continuous pulse oximetry
Measures oxygen levels right after birth; very low saturations reflect severe lung underdevelopment and airway problems. (This monitors severity rather than making the genetic diagnosis.)Cardiorespiratory monitoring (ECG and impedance)
Tracks heart rate and breathing effort; infants with AO2 often need intensive monitoring because of unstable breathing.Polysomnography or capnography (if survival allows)
In rare longer-term survivors, sleep or ventilatory studies assess airflow obstruction and CO₂ retention to guide support. (Supportive physiologic assessment consistent with severe thoracic restriction.)
E) Imaging Tests
Prenatal ultrasound
Shows very short long bones, narrow chest, and sometimes a cleft palate; these findings typically appear in the second trimester and raise strong suspicion for a lethal skeletal dysplasia such as AO2 or achondrogenesis IB. Orpha+1Postnatal full skeletal survey (X-rays)
Radiographs show incomplete ossification of long bones and spine, very short tubular bones, and characteristic hand–foot changes—an imaging pattern that, together with genetics, clinches the diagnosis. OrphaFetal MRI (selected cases)
If available, MRI can help evaluate lung volume and the airway, adding detail for delivery planning and counseling in high-risk pregnancies.
Non-Pharmacological Care (Supportive & Counseling Focus)
Because AO2 is perinatal-lethal and lacks disease-modifying therapy, non-drug care centers on accurate diagnosis, informed family choices, and compassionate neonatal support. (Each item states purpose and mechanism in plain English.)
Early, detailed prenatal ultrasound with skeletal survey
Purpose: Detect a severe skeletal dysplasia early so parents receive clear information.
Mechanism: Systematic measurements (long bone lengths, thoracic–abdominal ratios), hand/foot posture (hitchhiker thumb), and characteristic spine/pelvis features suggest a lethal dysplasia. Obstetrics & Gynecology+1Genetic counseling for the family
Purpose: Explain inheritance, recurrence risk (25%), and testing options in future pregnancies.
Mechanism: A trained counselor reviews SLC26A2 biology, interprets results, and supports decision-making. MedlinePlusDiagnostic molecular testing (fetus or neonate)
Purpose: Confirm AO2 and distinguish it from other dysplasias.
Mechanism: Sequencing SLC26A2 to find two pathogenic variants. PubMedMultidisciplinary perinatal care planning
Purpose: Align care with family goals (comfort-focused vs. intensive support), anticipate delivery needs.
Mechanism: Obstetrics, neonatology, anesthesia, genetics, and palliative care build a birth plan. Acta MedicaNeonatal palliative (comfort) care
Purpose: Prevent suffering and honor family wishes when survival is not expected.
Mechanism: Gentle handling, warmth, oxygen for comfort (not to prolong dying), and parental bonding support. Myriad GeneticsClear communication about limits of ventilation
Purpose: Avoid burdensome interventions that cannot reverse lung hypoplasia.
Mechanism: Explain that even intubation/ventilation often cannot oxygenate adequately due to tiny lungs. Fetal Medicine FoundationPsychosocial and bereavement support
Purpose: Support parental mental health during and after loss.
Mechanism: Counseling, memory-making, spiritual care if desired. Acta MedicaDocumentation for future reproductive planning
Purpose: Enable targeted carrier testing and early diagnosis next time.
Mechanism: Keep the exact SLC26A2 variants on file; offer testing to relatives if appropriate. MedlinePlusOption of chorionic villus sampling (CVS) or amniocentesis in future pregnancies
Purpose: Early molecular diagnosis when both parents are known carriers.
Mechanism: Test fetal DNA for the family’s two known SLC26A2 variants. MedlinePlusPreimplantation genetic testing (PGT-M) discussion
Purpose: Some families choose IVF with embryo testing to avoid recurrence.
Mechanism: Select embryos without both pathogenic variants for transfer. SCIRPAccurate differential diagnosis
Purpose: Separate AO2 from FLNB-related AO1/AO3 or other lethal dysplasias.
Mechanism: Gene-specific testing (SLC26A2 vs. FLNB) because “AO2” is SLC26A2-related, not FLNB-related. NCBI+1Ethical, culturally sensitive decision support
Purpose: Ensure choices reflect family values and local laws.
Mechanism: Neutral counseling with clear, jargon-free information about prognosis and options. Acta MedicaPostnatal evaluation for associated issues (if liveborn)
Purpose: Identify cleft palate feeding risks and airway fragility to minimize distress.
Mechanism: Gentle feeding strategies, positioning, and suctioning as comfort allows. MedlinePlusCare coordination and documentation
Purpose: Prevent repeated invasive procedures that do not change outcomes.
Mechanism: A shared plan in the chart specifying comfort-focused measures. Myriad GeneticsCommunity and patient-support resources
Purpose: Connect families with rare-disease information and survivor/parent networks.
Mechanism: Curated referrals (e.g., GARD, NORD) for education and peer support. Genetic & Rare Diseases Center
(Items would typically include speech/feeding therapy, orthoses, physiotherapy, and orthopedic planning; however, these are relevant to non-lethal SLC26A2 disorders like diastrophic dysplasia—not to AO2. Including them for AO2 would be misleading.) MDPI
Medicines
Crucial reality check: There is no disease-modifying drug for AO2. Reported medications are for comfort (e.g., analgesia) or standard neonatal care and do not change survival. Where possible, we draw on authoritative references stating the absence of specific therapy. PubMed+1
Analgesics (e.g., oral morphine drops or IV opioids in a NICU setting)
Class: Opioid analgesic. Dose/Time: Titrated by neonatologist for short-term comfort. Purpose: Relieve pain or air-hunger. Mechanism: μ-opioid receptor agonism reduces pain/dyspnea perception. Side effects: Sedation, respiratory depression—managed by careful dosing. Note: Comfort-focused use only; does not treat the underlying disease. PubMedAnxiolytic/sedative (e.g., midazolam in monitored settings)
Class: Benzodiazepine. Dose/Time: NICU protocols, brief use. Purpose: Ease severe distress. Mechanism: GABA-A potentiation. Side effects: Sedation, respiratory suppression; specialist-only use. PubMedAntisecretory/antireflux measures (e.g., H2 blockers as clinically indicated)
Class: Acid suppression. Purpose: Reduce reflux-associated discomfort if present. Mechanism: Lower gastric acidity. Limits: Symptomatic only. PubMedAntibiotics (only if clear infection)
Class: Antimicrobial. Purpose: Treat proven infections in standard neonatal fashion. Mechanism: Pathogen-targeted. Limits: No effect on AO2 itself. PubMedSurfactant/ventilation strategies
Note: Even with NICU-level support, profound lung hypoplasia means response is often poor; any such support is individualized and may be withheld if burdensome relative to expected benefit. Fetal Medicine Foundation
(Providing an artificial list of drugs with doses and schedules would be inappropriate for AO2 and could be unsafe. Authoritative sources emphasize that there is no specific therapy—management is supportive vs. palliative based on the infant’s condition and family goals.) PubMed+1
Dietary Molecular Supplements
There are no supplements proven to help AO2. Experimental work in mouse models of other SLC26A2 disorders (e.g., diastrophic dysplasia) has studied N-acetylcysteine (NAC) as a sulfate source to improve proteoglycan sulfation, but this is preclinical and not validated for AO2 in humans. Families should not rely on supplements in place of medical counseling. MDPI
N-Acetylcysteine (research context only)
Description: Antioxidant and cysteine donor; in animal studies, increases available sulfate for cartilage. Dose: No human neonatal AO2 dosing exists. Function/Mechanism: May increase proteoglycan sulfation in cartilage (shown in mice). Status: Experimental; not recommended for clinical use in AO2. MDPI
(Any additional “10-item” supplement list would be speculative and not evidence-based for AO2; therefore, not provided.)
Immunity-Booster / Regenerative / Stem-Cell Drugs
There are no immune boosters, regenerative drugs, or stem-cell therapies proven to treat or reverse AO2 in humans. AO2 results from a structural biosynthetic defect in cartilage sulfation due to SLC26A2 variants—not an immune problem. Gene or cell therapies remain theoretical and are not available clinically for AO2. PubMed
Surgeries
Because AO2 is perinatal-lethal, surgery is generally not indicated. Procedures that might be helpful in other, non-lethal SLC26A2 disorders (e.g., later orthopedic corrections) do not apply in AO2. Rarely, in a liveborn infant where families and clinicians agree on short-term life-prolonging efforts, limited procedures may be considered for comfort—but they do not change prognosis:
Airway stabilization/intubation (case-by-case): May temporarily support breathing but often cannot overcome lung under-development; burdens and benefits must be carefully weighed. Fetal Medicine Foundation
Feeding support for cleft palate (comfort-focused): Positioning and specialized nipples if feeding is attempted; invasive gastrostomy not typically chosen in AO2. MedlinePlus
Prevention
Carrier testing of both parents (and adult relatives if appropriate) to confirm the exact SLC26A2 variants. MedlinePlus
Early prenatal molecular testing (CVS or amniocentesis) for those variants in future pregnancies. MedlinePlus
Preimplantation genetic testing (PGT-M) during IVF to select embryos without both variants. SCIRP
Targeted early ultrasound in any subsequent pregnancy to detect severe skeletal signs. Obstetrics & Gynecology
Preconception counseling to plan timing, options, and supports. MedlinePlus
Accurate records of the family’s confirmed variants for fast future diagnosis. MedlinePlus
Consideration of local legal/ethical pathways relevant to pregnancy decisions. Acta Medica
Avoid misinformation—no proven supplements, diets, or “boosters” prevent AO2. MDPI
Use high-quality resources (MedlinePlus Genetics, GARD) for updates. MedlinePlus+1
Psychological support before, during, and after future pregnancies. Acta Medica
When to See Doctors
During pregnancy: If ultrasound shows very short limbs, small chest, or unusual thumb/foot positions, request referral to fetal medicine, genetics, and a tertiary NICU for counseling and diagnostic testing. Obstetrics & Gynecology
Preconception or early in a subsequent pregnancy: If you or your partner are known carriers, meet genetics early to plan CVS/amnio timing or PGT-M. MedlinePlus
What to Eat / What to Avoid
Because AO2 is a genetic cartilage-to-bone sulfation disorder, no maternal or infant diet can prevent or treat it. Eat a normal, healthy prenatal diet and follow obstetric guidance; avoid unproven “cures,” megadoses, or internet supplements claiming to fix skeletal dysplasias. PubMed+1
Frequently Asked Questions
1) Is AO2 the same as other “atelosteogenesis” types?
No. AO2 is caused by SLC26A2 variants (sulfate transporter). Atelosteogenesis types 1 and 3 are FLNB-related (filamin B) and are genetically distinct. NCBI
2) Can AO2 be cured with medicines or surgery?
No. Sadly, there is no curative treatment; care is supportive or palliative. PubMed+1
3) Can special foods, vitamins, minerals, or “immunity boosters” help?
No proven benefit. Do not substitute supplements for medical counseling. Experimental N-acetylcysteine helped mice with another SLC26A2 condition, but not AO2 in humans. MDPI
4) How is AO2 detected before birth?
Detailed ultrasound looking at bones and chest size, followed by genetic testing for SLC26A2 variants. Obstetrics & Gynecology+1
5) What causes the “hitchhiker thumb”?
Abnormal cartilage formation and joint development from impaired proteoglycan sulfation change thumb positioning. MedlinePlus
6) What’s the inheritance risk next time?
If both parents are carriers: 25% affected, 50% carrier, 25% unaffected in each pregnancy. MedlinePlus
7) Can we test early in a future pregnancy?
Yes—CVS (first trimester) or amniocentesis (second trimester) for the family’s known variants; PGT-M is also an option. MedlinePlus
8) Is AO2 related to diastrophic dysplasia?
Yes. Both are SLC26A2-related; AO2 is typically more severe and usually lethal, while diastrophic dysplasia is non-lethal. MedlinePlus
9) Why doesn’t ventilation save babies with AO2?
The lungs are too small (hypoplastic), so even with a ventilator there may not be enough functioning lung tissue to oxygenate. Fetal Medicine Foundation
10) Are there research directions?
Basic science explores ways to restore proteoglycan sulfation (e.g., sulfate donors in animals), but no approved human therapy exists for AO2. MDPI
11) Where can we read trustworthy information?
MedlinePlus Genetics and GARD provide reliable, plain-language summaries and references. MedlinePlus+1
12) How rare is AO2?
Extremely rare; the exact incidence is unknown. MedlinePlus
13) What decides between comfort care and intensive care?
Shared decision-making—after clear counseling about prognosis and likely burdens vs. benefits. Acta Medica
14) Could our families be carriers too?
Possibly—siblings of carriers may also carry the variant; they can seek genetic counseling/testing before family planning. MedlinePlus
15) Is AO2 ever misclassified as an FLNB disorder?
It can be clinically similar; that is why gene testing is essential to separate SLC26A2-AO2 from FLNB-AO1/AO3. NCBI
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The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members
Last Updated: September 25, 2025.
