Ataxia Telangiectasia

1. Clinical Overview

Summary

Ataxia telangiectasia (A-T) is a rare autosomal recessive neurodegenerative disorder caused by biallelic pathogenic mutations in the ATM (ataxia-telangiectasia mutated) gene located on chromosome 11q22-23. The ATM gene encodes a serine/threonine protein kinase that serves as a master regulator of the cellular response to DNA double-strand breaks, coordinating cell cycle checkpoints, DNA repair, and apoptosis. Loss of ATM function results in the accumulation of unrepaired DNA damage, leading to the multisystem manifestations that characterise A-T. [1]

The clinical hallmark is the classical triad of progressive cerebellar ataxia, oculocutaneous telangiectasias, and combined immunodeficiency. A-T typically presents in early childhood (age 1-4 years) with gait instability and truncal ataxia, though the pathognomonic telangiectasias often do not appear until age 5-8 years, potentially delaying diagnosis. The neurological phenotype is progressive and relentless, with most patients becoming wheelchair-dependent by adolescence (typically age 10-15 years). [2,3]

Beyond the classical triad, A-T is characterised by profound radiosensitivity, markedly increased cancer susceptibility (particularly lymphoid malignancies), recurrent sinopulmonary infections leading to bronchiectasis, endocrine abnormalities (growth failure, gonadal dysgenesis), and accelerated ageing features. The disorder exemplifies the critical importance of genome stability in neurological function, immune development, and cancer prevention. [4]

Life expectancy remains significantly reduced despite supportive care advances, with median survival of 19-25 years in classical A-T. The leading causes of death are respiratory failure (30-40%) from chronic lung disease and aspiration, and malignancy (30%). A subset of patients with hypomorphic ATM mutations manifest variant or milder A-T phenotypes with later onset, slower progression, and better survival. [5,6]

Key Facts

• Inheritance: Autosomal recessive (ATM gene on chromosome 11q22-23)
• Incidence: 1 in 40,000-100,000 live births worldwide [7]
• Carrier frequency: ~1% of general population (1 in 100)
• Classic Triad: Progressive cerebellar ataxia + Oculocutaneous telangiectasia + Combined immunodeficiency
• Cancer Risk: 38-fold increased overall; 100-250-fold for lymphoid malignancies [8]
• Radiosensitivity: Extreme cellular radiosensitivity; standard radiotherapy doses potentially fatal
• Median Survival: 19-25 years (classical A-T); longer in variant forms [5]
• Diagnostic Biomarker: Elevated serum alpha-fetoprotein (AFP) in >95% patients [9]
• Heterozygote Risk: ATM carriers have 2-3-fold increased breast cancer risk [10]

Clinical Pearls

The Delayed Triad: Telangiectasias typically appear at age 5-8 years, well after neurological onset. Early A-T (age 1-4) presents as isolated progressive cerebellar ataxia. Consider A-T in any child with progressive ataxia plus recurrent infections, even without visible telangiectasias.

The AFP Clue: Elevated serum AFP (>10 ng/mL after age 2 years) is present in >95% of A-T patients and is highly specific among the hereditary ataxias. An unexpectedly high AFP in a child with ataxia should prompt immediate consideration of A-T. AFP levels increase progressively with age in A-T patients. [9,11]

Radiation Danger — Document in Medical Records: A-T patients exhibit extreme radiosensitivity due to defective DNA double-strand break repair. Standard radiotherapy doses can cause catastrophic toxicity and death. Chemotherapy doses may also require modification. Prominent documentation in medical records is mandatory; consider medical alert bracelet. [12]

Oculomotor Apraxia as Early Clue: Oculomotor apraxia (difficulty initiating voluntary saccades, compensatory head thrusts) is often an early and prominent feature, sometimes preceding ataxia. This distinctive eye movement abnormality should raise suspicion for A-T.

Carrier Cancer Risk: Heterozygous ATM mutation carriers (1% of population) have increased cancer risk, particularly breast cancer (2-3-fold) and potentially other malignancies. Genetic counselling for family members is essential. [10,13]

Why This Matters Clinically

A-T is a paradigmatic disorder illustrating the fundamental importance of DNA repair in human health, with dysfunction affecting the nervous system, immune system, cancer surveillance, and multiple other organ systems. Early and accurate diagnosis is critical for several reasons:

Radiation Safety: Recognition prevents potentially fatal radiation exposure from diagnostic imaging or radiotherapy. A-T patients require modified cancer treatment protocols. [12]

Multidisciplinary Management: Coordinated care across neurology, immunology, pulmonology, oncology, endocrinology, and genetics optimises outcomes. Proactive infection prevention, aggressive treatment of respiratory infections, and pulmonary surveillance can slow progression to respiratory failure. [14]

Cancer Surveillance: Heightened clinical vigilance for lymphoma and leukaemia (which occur at 100-250-fold increased rates) enables earlier detection. If malignancy develops, treatment requires modification by specialist centres experienced in A-T. [8,15]

Genetic Counselling: Identification of ATM mutations permits carrier testing for family members, prenatal diagnosis for future pregnancies, and appropriate cancer surveillance for heterozygotes. [13]

Research and Trials: Accurate diagnosis enables enrolment in natural history studies and potential future therapeutic trials targeting ATM deficiency pathways or downstream consequences.

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2. Epidemiology

Incidence & Prevalence

Geographic and Ethnic Variation:

• Higher incidence in populations with consanguinity or founder mutations
• Specific founder mutations identified in Costa Rica, Moroccan Jews, Amish/Mennonite communities, and Polish populations
• True incidence may be underestimated due to diagnostic challenges and early mortality

Demographics

Risk Factors for A-T

Heterozygote (Carrier) Risks

Approximately 1% of the population carries one ATM mutation. Carrier status has been associated with:

• Breast cancer: 2-3-fold increased risk, particularly in truncating mutations [10,13]
• Contralateral breast cancer: Elevated risk in carriers with breast cancer [13]
• Other malignancies: Possible increased risk for gastric, pancreatic, and other cancers (data less consistent)
• Radiation sensitivity: Intermediate cellular radiosensitivity (between A-T patients and non-carriers)

Clinical implications include enhanced surveillance and management protocols for ATM heterozygotes with cancer. [13]

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3. Pathophysiology

Molecular Genetics

ATM Gene and Protein:

• Location: Chromosome 11q22-23
• Gene size: 150 kb spanning 66 exons
• Protein product: ATM kinase (3056 amino acids, 350 kDa)
• Protein structure: Member of phosphatidylinositol 3-kinase-related kinase (PIKK) family
• Functional domains: FAT (FRAP-ATM-TRRAP) domain, kinase domain, C-terminal FATC domain

Mutation Spectrum:

• Over 800 different pathogenic ATM mutations reported
• Classical A-T: Null mutations (nonsense, frameshift, splice-site) resulting in absent or severely truncated ATM protein
• Variant A-T: Missense mutations causing hypomorphic (reduced function) ATM protein [16]
• Genotype-phenotype correlation: Some correlation exists, with residual ATM kinase activity associated with milder phenotypes and better survival [6]

Mechanism of Disease

Step 1: DNA Double-Strand Break Detection

Under normal conditions, DNA double-strand breaks (DSBs) — the most cytotoxic form of DNA damage — activate the ATM signalling cascade:

1. DSBs are sensed by the MRN complex (MRE11-RAD50-NBS1)
2. MRN recruits and activates ATM at DSB sites
3. Inactive ATM exists as dimers/multimers; DSBs trigger autophosphorylation and monomerisation
4. Activated ATM phosphorylates >700 downstream substrates

Step 2: Defective DNA Damage Response in A-T

Without functional ATM, cells fail to mount appropriate responses to DSBs:

Step 3: Multi-System Pathophysiology

The defective DNA damage response manifests across organ systems:

Neurological Consequences

Cerebellar Degeneration:

• Progressive loss of cerebellar Purkinje cells and granule neurons
• Mechanism remains incompletely understood; hypotheses include:
  • Accumulation of oxidative DNA damage in post-mitotic neurons
  • Defective response to endogenous DNA lesions
  • Impaired mitochondrial function and increased reactive oxygen species
  • Neuroinflammatory processes [17]
• Cerebellar atrophy most prominent in vermis > hemispheres
• Brainstem nuclei and dorsal columns may be affected later

Extrapyramidal Features:

• Choreoathetosis, dystonia common
• Pathophysiology involves basal ganglia dysfunction, mechanism unclear

Peripheral Neuropathy:

• Axonal sensorimotor neuropathy develops in many patients
• Dorsal root ganglia and peripheral nerves show degeneration

Immunological Consequences

Thymic Hypoplasia and T-cell Deficiency:

• Thymus is markedly hypoplastic or absent
• V(D)J recombination (required for T-cell and B-cell receptor diversity) generates programmed DSBs
• Without ATM, these DSBs are poorly repaired → lymphocyte apoptosis
• Results in: lymphopenia (especially CD4+ T cells), poor T-cell proliferation, impaired cell-mediated immunity

B-cell and Antibody Deficiency:

• Defective B-cell development and class-switch recombination
• IgA deficiency (60-80% patients)
• IgG2/IgG4 subclass deficiencies (60-80%)
• Variable total IgG deficiency
• Poor specific antibody responses, especially to polysaccharide antigens [18]

Combined Immunodeficiency:

• A-T represents a combined (T and B cell) immunodeficiency
• Results in recurrent sinopulmonary infections (80% patients)
• Progressive chronic lung disease and bronchiectasis

Vascular Consequences

Telangiectasias:

• Dilated small blood vessels in conjunctivae, skin (ears, nose, flexural areas)
• Mechanism incompletely understood; may involve vascular endothelial dysfunction, chronic inflammation, defective angiogenesis regulation
• Typically appear age 5-8 years (often years after neurological onset)
• Not present in all A-T patients (~10% lack visible telangiectasias)

Malignancy Predisposition

Cancer Risk:

• 38-fold overall increased cancer risk [8]
• 100-250-fold increased risk for lymphoid malignancies (lymphoma, leukaemia)
• Mechanism: accumulation of unrepaired DNA damage → chromosomal instability → malignant transformation
• Characteristic chromosomal translocations involving chromosomes 7 and 14 (T-cell receptor and immunoglobulin loci)
• Increased solid tumour risk with age (breast, gastric, ovarian)

Radiosensitivity:

• ATM-deficient cells exhibit extreme sensitivity to ionising radiation
• Radiation induces DSBs; without ATM, these cannot be efficiently repaired
• Clinical consequence: standard radiotherapy doses cause catastrophic toxicity [12]
• Chemotherapy may also cause enhanced toxicity (agents causing DSBs)

Endocrine and Other Consequences

Classification of A-T Phenotypes

Genotype-phenotype correlations exist, with missense mutations allowing some residual ATM kinase activity associated with milder phenotypes and better survival. [6,16]

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4. Clinical Presentation

Timeline of Clinical Features

Neurological Features

Cerebellar Ataxia (100% of classical A-T):

• Presenting feature in vast majority: gait instability, frequent falls, truncal ataxia
• Progression: Truncal → appendicular → complete wheelchair dependence (median age ~12 years)
• Characteristics: Broad-based gait, dysmetria, intention tremor, dysdiadochokinesia, truncal titubation
• Relentless progression distinguishes A-T from non-progressive ataxias

Oculomotor Apraxia (>90%): [3]

• Difficulty initiating voluntary horizontal saccades
• Compensatory head thrust: Patient uses head movement to shift gaze
• Vertical saccades less affected
• Smooth pursuit usually preserved
• Highly characteristic of A-T; useful early diagnostic clue

Speech and Swallowing:

• Dysarthria: Progressive cerebellar dysarthria (scanning speech, irregular rhythm)
• Dysphagia: Develops with disease progression; aspiration risk increases
• Drooling common (oromotor dysfunction)

Extrapyramidal Features (50-80%):

• Choreoathetosis (involuntary writhing movements)
• Dystonia (sustained muscle contractions)
• Myoclonus (rare)
• May be mistaken for cerebral palsy in early childhood [3]

Peripheral Neuropathy (develops later):

• Axonal sensorimotor neuropathy
• Reduced or absent deep tendon reflexes (initially paradoxical with cerebellar signs)
• Distal sensory loss (vibration, proprioception)
• Contributes to gait impairment

Cognitive Function:

• Intelligence typically normal or near-normal in majority
• Some patients have mild learning difficulties or intellectual disability (~30%)
• Progressive neurological disability impairs academic performance despite preserved cognition
• Mood disorders (depression, anxiety) common, especially adolescence

Telangiectasias

Clinical Notes:

• Telangiectasias are not present at birth or in early childhood
• Delayed appearance (typically age 5-8 years) means early A-T presents without the "classic triad"
• ~10% of confirmed A-T patients never develop visible telangiectasias
• Telangiectasias are blanching, non-pulsatile, dilated capillaries/venules
• Do not bleed or cause functional problems (cosmetic only)

Immunological Features and Infections

Immunodeficiency Pattern: [18]

Infection Pattern:

• Recurrent sinopulmonary infections (80% patients) [18]
  • Recurrent otitis media, sinusitis, bronchitis, pneumonia
  • "Encapsulated bacteria common: Streptococcus pneumoniae, Haemophilus influenzae"
• Chronic lung disease:
  • Bronchiectasis develops from recurrent infections
  • Interstitial lung disease in some patients
  • Aspiration pneumonia (from dysphagia)
• Opportunistic infections: Less common than in severe combined immunodeficiency, but can occur

Pulmonary Manifestations: [19]

• Recurrent pneumonia → bronchiectasis (50-70% patients)
• Chronic cough, sputum production
• Restrictive lung disease (from ataxia affecting respiratory muscles)
• Aspiration (from progressive dysphagia)
• Respiratory failure is leading cause of death (30-40%) [5]

Growth and Endocrine Features

Dermatological Features

• Telangiectasias (see above)
• Café-au-lait macules: May be present (30%)
• Cutaneous granulomas: Occasionally seen
• Premature ageing: Greying hair, aged appearance (progeria-like)
• Vitiligo: Reported in some patients
• Eczema: May occur

Malignancy

Cancer Incidence and Types: [8,15]

Clinical Presentation of Malignancy:

• Lymphadenopathy (persistent, enlarging)
• Hepatosplenomegaly
• Unexplained cytopenias
• B symptoms (fever, night sweats, weight loss)
• Mediastinal mass on chest imaging

Treatment Challenges: [15]

• A-T patients with cancer have increased treatment-related toxicity
• Radiation therapy potentially fatal — generally contraindicated
• Chemotherapy doses may require reduction (especially alkylating agents)
• Infection risk heightened during chemotherapy
• Survival outcomes poorer than age-matched cancer patients without A-T
• Management requires specialist centres with A-T and oncology expertise

Red Flags — Urgent Investigation Required

[!CAUTION] Neurological Red Flags:

• Progressive ataxia in a child (especially age 1-5 years)
• Ataxia combined with recurrent infections
• Oculomotor apraxia (head thrust to initiate saccades)
• Combination of ataxia and choreoathetosis

Infection/Immunological Red Flags:

• Recurrent sinopulmonary infections with neurological signs
• Persistent or severe infections despite appropriate antibiotics
• Absent thymic shadow on chest X-ray with recurrent infections

Oncological Red Flags:

• Lymphoma or leukaemia in a patient with ataxia
• Unexplained lymphadenopathy or hepatosplenomegaly in A-T patient
• Persistent cytopenias, B symptoms

Iatrogenic Risk Red Flags:

• EXTREME radiation reaction (patient or family history of A-T should prompt avoidance)
• Severe chemotherapy toxicity in lymphoma/leukaemia patient

Respiratory Red Flags:

• Progressive dyspnoea, chronic cough, hypoxia
• Recurrent aspiration events
• Acute respiratory deterioration

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5. Clinical Examination

Structured Examination Approach

General Inspection:

• Short stature, low weight
• Aged/progeric appearance (premature greying, aged facies)
• Wheelchair or mobility aids (in older children/adolescents)
• Drooling, dysarthria on conversation
• Abnormal involuntary movements at rest (choreoathetosis)

Head and Neck:

Eyes — Oculomotor Examination: [3]

Oculomotor apraxia: Patient uses head thrust to shift gaze, as voluntary saccade initiation is impaired. Highly characteristic.

Neurological Examination — Cerebellar Function:

Neurological Examination — Extrapyramidal Features:

• Choreoathetosis: Involuntary writhing movements of fingers, hands, face
• Dystonia: Sustained abnormal postures (feet, hands)
• Myoclonus: Rare in A-T

Neurological Examination — Peripheral Nervous System:

Respiratory Examination:

Abdominal Examination:

• Hepatomegaly: Consider malignancy (lymphoma), rarely liver disease
• Splenomegaly: Lymphoma, infection, hypersplenism
• Masses: Lymphadenopathy, organomegaly

Skin Examination:

• Telangiectasias (see above)
• Café-au-lait macules (30%)
• Cutaneous granulomas
• Eczema, vitiligo

Growth Assessment:

• Height, weight (typically less than 3rd centile in majority)
• Tanner staging (delayed puberty common)

Special Examination Techniques

Oculomotor Apraxia Demonstration:

1. Ask patient to fixate on your nose
2. Present targets to left and right of midline
3. Ask patient to "look at my finger" (held 30-40° from midline)
4. Observe for: delayed saccade initiation, head thrust to move eyes, compensatory head movement

Dysmetria Assessment:

• Finger-nose test: Observe for past-pointing, intention tremor, decomposition of movement
• Heel-shin test: Assess lower limb coordination

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6. Investigations

Diagnostic Pathway

SUSPECTED A-T (progressive ataxia ± infections ± telangiectasias)
                       ↓
┌────────────────────────────────────────────────────┐
│  FIRST-LINE SCREENING TESTS                        │
│  • Serum alpha-fetoprotein (AFP)                   │
│  • Immunoglobulins (IgA, IgG, IgM, IgG subclasses) │
│  • Lymphocyte subsets (CD3, CD4, CD8, CD19)        │
│  • Chromosome breakage (if available)              │
└────────────────────────────────────────────────────┘
                       ↓
          AFP elevated (>10 ng/mL after age 2)?
                       ↓
┌────────────────────────────────────────────────────┐
│  CONFIRMATORY GENETIC TESTING                      │
│  • ATM gene sequencing (next-generation seq)       │
│  • Deletion/duplication analysis (MLPA/array CGH)  │
│  • Confirm biallelic pathogenic variants           │
└────────────────────────────────────────────────────┘
                       ↓
┌────────────────────────────────────────────────────┐
│  BASELINE INVESTIGATIONS                           │
│  • MRI brain (cerebellar atrophy)                  │
│  • Pulmonary function tests (if able)              │
│  • CT chest (bronchiectasis) — AVOID if possible   │
│  • Baseline bloods, cancer surveillance            │
└────────────────────────────────────────────────────┘

First-Line Screening Tests

Serum Alpha-Fetoprotein (AFP): [9,11]

• Interpretation: AFP >10 ng/mL after age 2 years in a child with progressive ataxia is highly suggestive of A-T
• AFP is not elevated in other hereditary ataxias (useful discriminator)
• AFP increases progressively with age in A-T patients
• Mechanism of AFP elevation in A-T remains unclear (liver origin, but no hepatic pathology)

Immunological Investigations: [18]

Vaccine Response Testing:

• Antibody responses to tetanus, diphtheria (protein antigens): Often normal or mildly impaired
• Antibody responses to pneumococcal polysaccharide (polysaccharide antigens): Frequently impaired
• Useful to assess functional antibody production

Confirmatory Genetic Testing

ATM Gene Analysis:

Genetic Counselling:

• Confirm biallelic pathogenic variants (one mutation from each parent)
• Carrier testing for parents and siblings
• Prenatal diagnosis available for future pregnancies
• ATM heterozygote cancer risk counselling [13]

Alternative Confirmatory Tests (if genetic testing unavailable/inconclusive):

Imaging

Brain MRI: [2]

• Cerebellar atrophy is progressive; repeat MRI over years shows worsening
• Early MRI may be normal or show only subtle vermian atrophy
• Atrophy does not correlate precisely with clinical severity

Chest Imaging: [19]

[!WARNING] Minimise Ionising Radiation: A-T patients are exquisitely radiosensitive. Use MRI and ultrasound preferentially. If CT is essential, use low-dose protocols and minimise repeat scans. Document radiation sensitivity prominently in medical records.

Other Imaging:

• Ultrasound abdomen: Assess organomegaly (hepatosplenomegaly if malignancy suspected)
• Echocardiography: Baseline cardiac assessment if indicated

Baseline and Monitoring Laboratory Tests

Pulmonary Function Testing

• Many young children with A-T cannot cooperate with spirometry due to ataxia and cognitive factors
• Serial testing (if feasible) monitors progression

Cancer Surveillance Investigations

Routine Surveillance (currently no consensus guidelines):

If Malignancy Suspected:

• Lymph node biopsy (excisional preferred over needle)
• Bone marrow examination
• Staging imaging (MRI/ultrasound preferred; avoid CT/PET-CT if possible)
• Liaise with A-T specialist centre and oncologist experienced in A-T

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7. Differential Diagnosis

Differential Diagnosis of Progressive Ataxia in Childhood

Key Discriminators:

• Elevated AFP: A-T, AOA2 (but AOA2 has normal immunoglobulins)
• Telangiectasias: A-T (pathognomonic)
• Oculomotor apraxia: A-T, AOA1, AOA2, ATLD
• Immunodeficiency: A-T
• Progressive vs non-progressive: A-T is relentlessly progressive

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8. Management

Management Principles

A-T is a multisystem disorder requiring coordinated multidisciplinary care. There is no curative treatment; management is supportive, focusing on:

1. Preventing and treating infections (immunodeficiency)
2. Maintaining respiratory health (preventing/managing bronchiectasis)
3. Optimising mobility and function (rehabilitation)
4. Cancer surveillance and modified treatment if malignancy develops
5. Managing endocrine, nutritional, and other complications
6. Avoiding radiation exposure
7. Genetic counselling and family support

Specialist Centre Involvement:

• A-T management is optimally delivered by specialist centres with multidisciplinary A-T clinics
• Coordination between local and specialist services

Multidisciplinary Team

Infection Prevention and Treatment

Prophylactic Antimicrobials: [14,18]

Immunoglobulin Replacement Therapy (IVIG or SCIG):

Vaccinations: [14]

Prompt Treatment of Infections:

• Low threshold for antibiotics for respiratory infections
• Prolonged courses may be needed (bronchiectasis, slow immune response)
• Empiric broad-spectrum antibiotics for significant infections
• Monitor for complications (empyema, sepsis)

Pulmonary Management

Airway Clearance: [14,19]

Monitoring Pulmonary Function:

• Serial spirometry (if able to perform)
• Oxygen saturation monitoring
• Sleep study if nocturnal hypoventilation suspected

Management of Respiratory Failure: [19]

• Non-invasive ventilation (NIV): Bi-level positive airway pressure (BiPAP) for nocturnal hypoventilation or respiratory failure
• Supplemental oxygen: For hypoxia
• Invasive ventilation: Consider in acute deterioration; prognosis discussions essential
• Tracheostomy: Rarely used; consider in severe chronic respiratory failure with good quality of life otherwise

Aspiration Precautions:

• Swallowing assessment by speech therapist
• Modified diet (thickened fluids, soft foods)
• Positioning during feeds
• Consider gastrostomy if oral intake unsafe/inadequate

Neurological and Rehabilitation Management

Physiotherapy:

• Maintain mobility as long as possible
• Strengthening exercises
• Balance training (within limitations)
• Fall prevention strategies
• Gait aids (walker, canes)
• Wheelchair provision (typically age 10-15 years)

Occupational Therapy:

• Activities of daily living (ADLs) training
• Adaptive equipment (eating utensils, dressing aids)
• Home modifications (ramps, bathroom adaptations)
• Seating and positioning (wheelchair seating clinic)

Speech and Language Therapy:

• Dysarthria management (speech exercises, communication strategies)
• Augmentative and alternative communication (AAC) if speech deteriorates
• Dysphagia management (see aspiration precautions above)

Symptomatic Treatments:

Experimental Neuroprotective Strategies:

• No proven neuroprotective treatments for A-T currently
• Clinical trials exploring antioxidants, anti-inflammatory agents, ATM-independent pathways
• Preclinical data on ibuprofen, N-acetylcysteine, EGb-761 (Ginkgo biloba extract) — not yet proven in humans [17]

Cancer Surveillance and Management

Surveillance Strategy: [8,15]

Management of Malignancy in A-T: [15]

[!CAUTION] MODIFIED CANCER TREATMENT PROTOCOLS ESSENTIAL

A-T patients with malignancy require specialist management:

• Radiotherapy generally contraindicated (potentially fatal toxicity)
• Chemotherapy doses may require reduction (alkylating agents, others causing DNA damage)
• Increased infection risk (pre-existing immunodeficiency + chemotherapy)
• Higher treatment-related mortality
• Multidisciplinary planning involving A-T specialists, oncologists, immunologists

Treatment Modifications:

• Avoid radiotherapy unless absolutely no alternative (discuss with A-T specialist centre)
• Reduce chemotherapy doses (often 50-70% standard doses for alkylating agents, anthracyclines)
• Enhance infection prophylaxis during treatment (IVIG, G-CSF, antimicrobial prophylaxis)
• Manage complications aggressively (febrile neutropenia, mucositis, etc.)
• Consider reduced-intensity regimens if curative intent not achievable

Prognosis with Malignancy:

• A-T patients with cancer have poorer survival than age-matched non-A-T cancer patients [15]
• Treatment-related mortality significant
• Shared decision-making with family regarding treatment intensity

Endocrine and Growth Management

Nutritional Management

Radiation Avoidance — Critical Safety Measure

[!WARNING] RADIATION SAFETY PROTOCOL:

1. Document prominently in medical records: "ATAXIA-TELANGIECTASIA — EXTREME RADIOSENSITIVITY — AVOID UNNECESSARY IONISING RADIATION"
2. Medical alert bracelet: Patient should wear identification noting A-T and radiosensitivity
3. Imaging hierarchy:
   • First choice: Ultrasound, MRI (no ionising radiation)
   • If CT essential: Low-dose protocol, minimise scans
   • Nuclear medicine scans: Minimise; discuss risk-benefit
   • Radiotherapy: Generally contraindicated; discuss with A-T specialist if absolutely necessary
4. Cancer treatment: Modified protocols (see above) [12]
5. Educate family and patient: Inform of radiation risk; empower to question unnecessary imaging

Genetic Counselling and Family Management

For Affected Individual:

• Explain autosomal recessive inheritance
• Implications for siblings (25% recurrence risk per pregnancy)
• Fertility generally markedly reduced or absent (gonadal failure)

For Parents:

• Both parents are obligate carriers (heterozygotes)
• 25% recurrence risk in each future pregnancy
• Prenatal diagnosis available: Chorionic villus sampling or amniocentesis for ATM mutation analysis
• Preimplantation genetic diagnosis (PGD): Available in some centres

For Siblings: [13]

• 50% chance of being a carrier
• 25% chance of being affected (if symptomatic, likely already diagnosed)
• 25% chance of being unaffected and non-carrier
• Offer carrier testing (especially if planning children)
• Carriers: Increased cancer risk (especially breast cancer in females); consider enhanced surveillance

ATM Heterozygote Cancer Surveillance: [13]

• Breast cancer: Consider enhanced screening (annual mammography/MRI from age 40, or earlier based on family history)
• Other cancers: Data less clear; individualised approach

Supportive and Palliative Care

Psychosocial Support:

• A-T is progressive and life-limiting; psychological support for patient and family essential
• Peer support groups (A-T societies, patient organisations)
• School support (educational plans, accessibility)

Advanced Care Planning:

• As disease progresses, discuss preferences for invasive interventions (intubation, resuscitation)
• Palliative care involvement for symptom management
• Quality of life focus in advanced disease

End-of-Life Care:

• Respiratory failure most common terminal pathway
• Symptom management: dyspnoea (opioids, oxygen), secretions (anticholinergics), anxiety (benzodiazepines)
• Hospice or home-based palliative care

Emerging and Experimental Therapies

Current Research Directions:

1. ATM-independent DNA repair pathways: Enhancing alternative repair mechanisms
2. Antioxidants: Reducing oxidative stress (e.g., N-acetylcysteine, EGb-761)
3. Anti-inflammatory agents: Reducing neuroinflammation (e.g., ibuprofen — preclinical promise) [17]
4. Read-through agents: For nonsense mutations (e.g., ataluren) — investigational
5. Stem cell transplantation: Haematopoietic stem cell transplant (HSCT) for immunodeficiency — very limited data, high risk, not standard [20]
6. Gene therapy: Preclinical development

Clinical Trials:

• Patients and families should be informed of ongoing trials
• Registration in natural history studies (A-T Clinical Research Network, others)

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9. Complications

Respiratory Complications

Oncological Complications

Neurological Complications

Endocrine and Metabolic Complications

Infection-Related Complications

Iatrogenic Complications

[!CAUTION] Radiation-Induced Toxicity: [12]

• Severe reactions to radiotherapy (skin necrosis, organ damage, death)
• Even diagnostic radiation (repeated CTs) may have cumulative effects
• Prevention: Avoid unnecessary radiation; document radiosensitivity prominently

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10. Prognosis & Outcomes

Natural History

A-T is a progressive neurodegenerative disorder with multisystem involvement and reduced life expectancy. The natural history follows a relatively predictable trajectory in classical A-T, though variant forms may have slower progression.

Typical Progression:

Life Expectancy

Classical A-T: [5,6]

• Median survival: 19-25 years
  • "Historical cohorts: ~19 years"
  • "Recent cohorts (improved care): up to 25 years"
• Range: Some patients die in early childhood (severe infections, malignancy); others survive into 30s with excellent care
• Improving trend: Survival has improved with better infection management, respiratory care, and multidisciplinary support

Variant/Mild A-T: [16]

• Median survival: Potentially into 4th-5th decade (30s-40s)
• Some patients with hypomorphic mutations have survived to 50s-60s
• Later onset, slower progression, milder immunodeficiency

Causes of Death

Prognostic Factors

Better Prognosis: [6,16]

• Variant A-T phenotype (hypomorphic mutations with residual ATM activity)
• Later onset of symptoms
• Milder immunodeficiency
• Access to multidisciplinary specialist care [14]
• Absence of malignancy
• Good respiratory function and proactive pulmonary care [19]

Poorer Prognosis: [5,6]

• Classical A-T (null mutations, no ATM protein)
• Early onset (age less than 2 years)
• Severe immunodeficiency (very low IgG, severe lymphopenia)
• Development of malignancy [15]
• Chronic lung disease/bronchiectasis [19]
• Poor access to specialist care

Genotype-Phenotype Correlation:

• Patients with missense mutations allowing some residual ATM kinase activity tend to have milder phenotypes and longer survival [6,16]
• Patients with truncating mutations (nonsense, frameshift) typically have classical severe phenotype
• Correlation not absolute; modifying factors likely exist

Quality of Life

Preserved Cognition:

• Intelligence typically normal or near-normal in majority
• Patients are aware of their progressive disability
• Psychological support essential (depression, anxiety common)

Impact on Daily Living:

• Progressive loss of independence: mobility, self-care, feeding
• Communication difficulties: dysarthria, anarthria in late stages
• Fatigue: chronic illness, infections, respiratory disease
• Social isolation: school difficulties, peer relationships, mobility limitations

Positive Factors:

• Strong family and community support
• Access to adaptive equipment and technology
• Educational accommodations
• Peer support through A-T patient organisations

Patient-Reported Outcomes:

• Younger children often unaware of severity/prognosis; may be relatively content
• Adolescents and young adults often struggle with awareness of progressive nature and reduced life expectancy
• Psychosocial support, counselling, and palliative care involvement can improve quality of life

Outcome with Interventions

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11. Evidence & Guidelines

Key Guidelines

International and National Guidelines:

1. Rothblum-Oviatt C, et al. (2016) — Ataxia telangiectasia: a review. Orphanet J Rare Dis. [1]

   • Comprehensive review and consensus recommendations
   • Covers diagnosis, clinical features, management across specialties
   • Widely cited as authoritative A-T reference

2. Bhatt JM, et al. (2015) — ERS statement on the multidisciplinary respiratory management of ataxia telangiectasia. Eur Respir Rev. [14]

   • European Respiratory Society evidence-based guidelines for pulmonary management
   • Recommendations on airway clearance, infection prevention, monitoring, NIV
   • Multidisciplinary approach to respiratory care

3. van Os NJ, et al. (2016) — Health risks for ataxia-telangiectasia mutated heterozygotes: a systematic review, meta-analysis and evidence-based guideline. Clin Genet. [13]

   • Evidence-based guideline for ATM carrier cancer risk and surveillance
   • Systematic review and meta-analysis of heterozygote cancer risk
   • Recommendations for breast cancer screening in ATM carriers

4. Nowak-Wegrzyn A, et al. (2004) — Immunodeficiency and infections in ataxia-telangiectasia. J Pediatr. [18]

   • Detailed analysis of immunological features and infection patterns
   • Recommendations for immunological assessment and management

5. A-T Society (UK) Clinical Care Guidance (available at www.atsociety.org.uk)

   • Patient organisation guidelines for A-T management
   • Practical advice for families and clinicians

Landmark Studies and Key Evidence

Pathophysiology and Molecular Biology:

6. Micol R, et al. (2011) — Morbidity and mortality from ataxia-telangiectasia are associated with ATM genotype. J Allergy Clin Immunol. [6]

   • Demonstrated genotype-phenotype correlation: missense mutations → milder phenotype, better survival
   • 55 patients; median survival 25 years (missense) vs 18 years (truncating)

7. Shiloh Y, Lederman HM (2017) — Ataxia-telangiectasia (A-T): An emerging dimension of premature ageing. Ageing Res Rev.

   • Review of ATM's role beyond DNA repair; implications for ageing, metabolic dysfunction

Clinical Phenotype:

8. Suarez F, et al. (2015) — Incidence, presentation, and prognosis of malignancies in ataxia-telangiectasia: a report from the French national registry of primary immune deficiencies. J Clin Oncol. [8]

   • Large cohort (371 A-T patients)
   • 38-fold increased cancer risk overall; 100-250-fold for lymphoid malignancies
   • 25-30% cumulative cancer incidence by age 25

9. Stray-Pedersen A, et al. (2007) — Alpha fetoprotein is increasing with age in ataxia-telangiectasia. Eur J Paediatr Neurol. [11]

   • Demonstrated progressive increase in AFP with age in A-T patients
   • AFP >10 ng/mL in >95% patients after age 2 years

10. Schon K, et al. (2019) — Genotype, extrapyramidal features, and severity of variant ataxia-telangiectasia. Ann Neurol. [16]

    • Characterised variant A-T phenotypes
    • Extrapyramidal features common; genotype correlates with severity

Immunology and Infections:

11. Nowak-Wegrzyn A, et al. (2004) — Immunodeficiency and infections in ataxia-telangiectasia. J Pediatr. [18]
    • Detailed immunological phenotyping of 100 A-T patients
    • IgA deficiency 60-80%, IgG subclass deficiencies common, lymphopenia 70-90%
    • 80% had recurrent sinopulmonary infections

Pulmonary:

12. McGrath-Morrow SA, et al. (2010) — Evaluation and management of pulmonary disease in ataxia-telangiectasia. Pediatr Pulmonol. [19]

    • Review of pulmonary manifestations and management strategies
    • Bronchiectasis 50-70%; restrictive lung disease; aspiration

13. Bhatt JM, et al. (2015) — ERS statement on the multidisciplinary respiratory management of ataxia telangiectasia. Eur Respir Rev. [14]

    • Evidence-based respiratory management guidelines
    • Airway clearance, infection prevention, monitoring

Radiosensitivity:

14. Chun HH, Gatti RA (2004) — Ataxia-telangiectasia, an evolving phenotype. DNA Repair (Amst). [12]
    • Review of radiosensitivity in A-T
    • Cellular mechanisms and clinical implications

Cancer Treatment:

15. Magnarelli A, et al. (2025) — Prevalence and outcomes of cancer and treatment-associated toxicities for patients with ataxia telangiectasia. J Allergy Clin Immunol. [15]
    • Recent analysis of cancer treatment outcomes in A-T
    • Increased treatment-related toxicity; importance of modified protocols

Heterozygote Cancer Risk:

16. Yadav S, et al. (2023) — Contralateral Breast Cancer Risk Among Carriers of Germline Pathogenic Variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2. J Clin Oncol. [10]

    • Large study of cancer risks in ATM heterozygotes
    • Increased contralateral breast cancer risk in carriers

17. van Os NJ, et al. (2016) — Health risks for ataxia-telangiectasia mutated heterozygotes. Clin Genet. [13]

    • Systematic review: 2.3-fold increased breast cancer risk in ATM carriers
    • Recommendations for enhanced surveillance

Experimental Therapies:

18. Hui CW, et al. (2018) — Ibuprofen prevents progression of ataxia telangiectasia symptoms in ATM-deficient mice. J Neuroinflammation. [17]
    • Preclinical study: ibuprofen reduced neurodegeneration in A-T mouse model
    • Mechanism: anti-inflammatory (not yet proven in humans)

Evidence Strength Summary

Evidence Gaps:

• No randomised controlled trials for most A-T interventions (due to rarity)
• Evidence largely from case series, cohort studies, expert consensus
• Long-term outcomes with IVIG, prophylactic antibiotics not well-defined
• Optimal cancer surveillance strategy uncertain
• No proven neuroprotective or disease-modifying therapies

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12. Patient/Layperson Explanation

What is Ataxia Telangiectasia?

Ataxia telangiectasia (often called "A-T" for short) is a rare genetic condition that affects several parts of the body. It is caused by a fault (mutation) in a gene called ATM. This gene normally helps cells repair damage to their DNA (the instruction manual inside every cell). When the ATM gene doesn't work properly, cells cannot repair DNA damage, which leads to problems in the brain, immune system, and other parts of the body.

A-T is inherited (passed down from parents). Both parents must carry the faulty gene for a child to have A-T. Parents who carry one faulty gene are called "carriers" — they are healthy but can pass the gene to their children.

What are the main features of A-T?

A-T is named after its two main visible features:

1. Ataxia: Difficulty with balance and coordination
2. Telangiectasia: Tiny red blood vessels visible on the eyes and skin

The condition also affects the immune system, making it harder to fight infections.

The three main problems in A-T:

1. Movement and balance problems (ataxia):

   • Children with A-T usually start having trouble with balance and walking between ages 1 and 4 years
   • They may fall frequently and have difficulty coordinating movements
   • As time goes on, balance problems get worse
   • Most children need a wheelchair by their teenage years (usually around age 10-15)
   • Speech may become difficult (slurred or unclear)
   • Swallowing may become difficult later on

2. Tiny red blood vessels on eyes and skin (telangiectasias):

   • These are small, visible blood vessels that look like red threads
   • They appear on the white part of the eyes (usually around age 5-8 years)
   • They may also appear on the ears, nose, and other parts of the skin
   • They do not hurt or bleed — they are just a visible sign of A-T

3. Weak immune system and frequent infections:

   • The immune system does not work properly in A-T
   • This means children get frequent chest and sinus infections
   • Repeated lung infections can damage the lungs over time
   • Some children need regular antibiotics to prevent infections

What other problems can A-T cause?

• Increased cancer risk: People with A-T have a higher risk of developing certain cancers, especially leukaemia and lymphoma (cancers of the blood or immune system)
• Sensitivity to radiation: People with A-T are very sensitive to X-rays and radiation treatment. It is important to avoid unnecessary X-rays and CT scans
• Growth and puberty: Many children with A-T are shorter than average and may have delayed puberty
• Diabetes: Some people with A-T develop diabetes (high blood sugar)
• Lung problems: Repeated infections can lead to lung scarring and breathing difficulties

How is A-T diagnosed?

Doctors diagnose A-T by:

• Blood tests: A protein called alpha-fetoprotein (AFP) is usually high in A-T. Immune system tests often show low levels of certain antibodies
• Genetic testing: A blood test can look for mutations in the ATM gene. Finding two faulty copies of the gene confirms the diagnosis
• Brain scan (MRI): This may show shrinkage (atrophy) of part of the brain called the cerebellum, which controls balance

How is A-T treated?

There is no cure for A-T yet, but treatment can help with the symptoms and improve quality of life:

1. Preventing and treating infections:

   • Antibiotics to prevent chest infections (often taken 3 times a week)
   • Immunoglobulin infusions (IVIG) — giving antibodies through a drip to help the immune system fight infections
   • Vaccines (but NOT live vaccines like MMR in some cases — discuss with your doctor)
   • Treating infections quickly with antibiotics

2. Chest physiotherapy:

   • Daily exercises and techniques to clear mucus from the lungs
   • Helps prevent lung infections and keeps lungs healthy

3. Physiotherapy and occupational therapy:

   • Exercises to maintain strength and balance
   • Equipment to help with daily activities (walking aids, wheelchairs, adapted eating utensils)
   • Home modifications (ramps, bathroom adaptations)

4. Speech and swallowing therapy:

   • Help with unclear speech
   • Safe swallowing strategies to prevent choking
   • In some cases, a feeding tube may be needed if swallowing becomes unsafe

5. Avoiding radiation:

   • Very important: People with A-T are extremely sensitive to radiation
   • Avoid unnecessary X-rays and CT scans — use MRI or ultrasound instead
   • Never use radiotherapy (radiation treatment for cancer) unless absolutely no other option
   • Wear a medical alert bracelet noting A-T and radiation sensitivity

6. Cancer surveillance:

   • Regular check-ups to look for signs of cancer (swollen lymph nodes, blood tests)
   • If cancer develops, treatment must be carefully adjusted (lower doses, avoid radiation)

7. Support for growth and puberty:

   • Hormone replacement if puberty is delayed
   • Nutritional support to maintain weight and strength

What to expect — Living with A-T

• A-T is a progressive condition, meaning it gets worse over time
• Most children will need a wheelchair by their teenage years
• Breathing problems and infections become more common as time goes on
• Life expectancy is shorter than normal — most people with A-T live into their late teens or twenties, though some live longer with good care
• Intelligence is usually normal — children with A-T can go to school and learn (though physical disabilities may make this harder)

When to seek urgent medical help

Contact your doctor or go to the hospital urgently if:

• Breathing difficulties (fast breathing, shortness of breath, blue lips)
• Fever with cough or difficulty breathing (could be a serious infection)
• Difficulty swallowing or choking frequently
• Unusual lumps (swollen lymph nodes) or unexplained weight loss
• Unusual tiredness, bruising, or paleness (could be signs of leukaemia)

Support and resources

Living with A-T is challenging, but support is available:

• A-T Society (UK): www.atsociety.org.uk — patient support organisation
• A-T Children's Project (USA): www.atcp.org — research and family support
• Local support groups: Ask your doctor or specialist nurse about local groups
• Genetic counselling: For family planning and understanding inheritance
• Specialist A-T clinics: Multidisciplinary care at specialist centres

Important messages for families

• You are not alone: A-T is rare, but there are families and organisations who understand and can help
• Early diagnosis helps: Knowing the diagnosis allows you to get the right care and avoid radiation
• Quality of life matters: Even though A-T is progressive, good care can help your child live as fully as possible
• Advocate for your child: Make sure all doctors know about A-T and the need to avoid radiation
• Research is ongoing: Scientists are working on new treatments for A-T

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13. References

Primary Sources

1. Rothblum-Oviatt C, Wright J, Lefton-Greif MA, et al. Ataxia telangiectasia: a review. Orphanet J Rare Dis. 2016;11:159. PMID: 27884168. DOI: 10.1186/s13023-016-0543-7

2. Jackson TJ, Chow G, Suri M, et al. Longitudinal analysis of the neurological features of ataxia-telangiectasia. Dev Med Child Neurol. 2016;58(7):690-697. PMID: 26896183. DOI: 10.1111/dmcn.13052

3. Amirifar P, Ranjouri MR, Yazdani R, et al. Ataxia-telangiectasia: A review of clinical features and molecular pathology. Pediatr Allergy Immunol. 2019;30(3):277-288. PMID: 30685876. DOI: 10.1111/pai.13020

Molecular and Genetic Studies

4. Shiloh Y, Rotman G. Ataxia-telangiectasia and the ATM gene: linking neurodegeneration, immunodeficiency, and cancer to cell cycle checkpoints. J Clin Immunol. 1996;16(5):254-260. PMID: 8886993

5. Micol R, Ben Slama L, Suarez F, et al. Morbidity and mortality from ataxia-telangiectasia are associated with ATM genotype. J Allergy Clin Immunol. 2011;128(2):382-389. PMID: 21665257. DOI: 10.1016/j.jaci.2011.03.052

6. Schon K, van Os NJH, Oscroft N, et al. Genotype, extrapyramidal features, and severity of variant ataxia-telangiectasia. Ann Neurol. 2019;85(2):170-180. PMID: 30549301. DOI: 10.1002/ana.25394

Epidemiology

7. Swift M, Morrell D, Massey RB, Chase CL. Incidence of cancer in 161 families affected by ataxia-telangiectasia. N Engl J Med. 1991;325(26):1831-1836. PMID: 1961222

Cancer Risk and Outcomes

8. Suarez F, Mahlaoui N, Canioni D, et al. Incidence, presentation, and prognosis of malignancies in ataxia-telangiectasia: a report from the French national registry of primary immune deficiencies. J Clin Oncol. 2015;33(2):202-208. PMID: 25488969. DOI: 10.1200/JCO.2014.56.5101

9. Stray-Pedersen A, Borresen-Dale AL, Paus E, Lindman CR, Burgers T, Abrahamsen TG. Alpha fetoprotein is increasing with age in ataxia-telangiectasia. Eur J Paediatr Neurol. 2007;11(6):375-380. PMID: 17540590. DOI: 10.1016/j.ejpn.2007.04.001

10. Yadav S, Hu C, Nathanson KL, et al. Contralateral Breast Cancer Risk Among Carriers of Germline Pathogenic Variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2. J Clin Oncol. 2023;41(9):1703-1713. PMID: 36623243. DOI: 10.1200/JCO.22.01239

Radiosensitivity

11. Chun HH, Gatti RA. Ataxia-telangiectasia, an evolving phenotype. DNA Repair (Amst). 2004;3(8-9):1187-1196. PMID: 15279807. DOI: 10.1016/j.dnarep.2004.04.010

12. Painter RB, Young BR. Radiosensitivity in ataxia-telangiectasia: a new explanation. Proc Natl Acad Sci U S A. 1980;77(12):7315-7317. PMID: 6938978

Heterozygote Cancer Risk

13. van Os NJ, Roeleveld N, Weemaes CM, et al. Health risks for ataxia-telangiectasia mutated heterozygotes: a systematic review, meta-analysis and evidence-based guideline. Clin Genet. 2016;90(2):105-117. PMID: 26662178. DOI: 10.1111/cge.12710

Management Guidelines

14. Bhatt JM, Bush A, van Gerven M, et al. ERS statement on the multidisciplinary respiratory management of ataxia telangiectasia. Eur Respir Rev. 2015;24(138):565-581. PMID: 26621971. DOI: 10.1183/16000617.0066-2015

15. Magnarelli A, Dorsey MJ, Hanson IC, et al. Prevalence and outcomes of cancer and treatment-associated toxicities for patients with ataxia telangiectasia. J Allergy Clin Immunol. 2025;155(2):438-447. PMID: 39521281. DOI: 10.1016/j.jaci.2024.10.023

Immunology and Infections

16. Nowak-Wegrzyn A, Crawford TO, Winkelstein JA, Carson KA, Lederman HM. Immunodeficiency and infections in ataxia-telangiectasia. J Pediatr. 2004;144(4):505-511. PMID: 15069401. DOI: 10.1016/j.jpeds.2003.12.046

Experimental Therapies

17. Hui CW, Vecchiarelli HA, Gervais É, Luo X, Michaud F, Scheefhals L, et al. Ibuprofen prevents progression of ataxia telangiectasia symptoms in ATM-deficient mice. J Neuroinflammation. 2018;15(1):308. PMID: 30400801. DOI: 10.1186/s12974-018-1338-7

Pulmonary Management

18. McGrath-Morrow SA, Gower WA, Rothblum-Oviatt C, et al. Evaluation and management of pulmonary disease in ataxia-telangiectasia. Pediatr Pulmonol. 2010;45(9):847-859. PMID: 20583220. DOI: 10.1002/ppul.21277

19. Bott L, Lebreton J, Thumerelle C, Cuvellier J, Deschildre A, Sardet A. Lung disease in ataxia-telangiectasia. Acta Paediatr. 2007;96(7):1021-1024. PMID: 17524020. DOI: 10.1111/j.1651-2227.2007.00338.x

Biomarkers

20. Huang Y, Yang Z, Song F, et al. Twelve novel ATM mutations identified in Chinese ataxia telangiectasia patients. Neuromolecular Med. 2013;15(3):536-543. PMID: 23807571. DOI: 10.1007/s12017-013-8240-3

Additional Resources

21. Nissenkorn A, Ben-Zeev B. Ataxia telangiectasia. Handb Clin Neurol. 2015;132:199-214. PMID: 26564081. DOI: 10.1016/B978-0-444-62702-5.00014-7

22. Stankovic T, Kidd AM, Sutcliffe A, et al. ATM mutations and phenotypes in ataxia-telangiectasia families in the British Isles: expression of mutant ATM and the risk of leukemia, lymphoma, and breast cancer. Am J Hum Genet. 1998;62(2):334-345. PMID: 9463314

23. Taylor AMR, Metcalfe JA, Thick J, Mak YF. Leukemia and lymphoma in ataxia telangiectasia. Blood. 1996;87(2):423-438. PMID: 8555463

24. Fiévet A, Bellanger D, Rieunier G, et al. Functional classification of ATM variants in ataxia-telangiectasia patients. Hum Mutat. 2019;40(10):1713-1730. PMID: 31050087. DOI: 10.1002/humu.23778

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Last Reviewed: 2026-01-09 | MedVellum Editorial Team

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Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists for A-T management. A-T is a complex multisystem disorder requiring specialist multidisciplinary care.