Dr Varsha v s, Dr Vaishak Anand,Dr Praveena Bhaskaran ,DrC Jayakumar
Six year old girl child,presented with the complaints of speech difficulty, gait ataxia and progressive dystonia of the right side ,postural instability of 2 yrs duration. She was evaluated outside with EEG which was told to be abnormal and started on phenytoin and leviteracetam .
MRI showed cerebellar atrophy and she was referred to AIMS for a prompt diagnosis and management.
Background: Antenatal period was uneventful. Ba was borne Term/ CIAB/ Bwt: 3.3 kg/ NVD. Post natally uneventful. Developmentally appropriate for age till 4 years. Studying in 1st standard – good in studies.
On examination: Vitals stable.
Auxology: Wt :15.9 kg (3rd – 10th centile), Ht :109 cm (3rd – 10th centile), HC :50.5 cm.
Head to foot examination:
Telengiectasia conjunctiva, hypopigmented lesion back 2x 1 cm with multiple small hyperpigmented macules of chest, abdomen and back. Ocular telengiectasia ++ both eyes medial and lateral.
System examination: Neurology examination revealed hypometric saccades and broken pursuits, dystonic speech, no oculomotor apraxia , Neck and trunk with right sided limb dystonia, reflexes were sluggish ,mild past pointing and tandem walking- mild difficulty and Gait -narrow base with tendency to toe-walking were seen.
Evaluation: Blood routines were normal. AFP was 315 and IgA was less than 5 mg /dl (low ) and IgM was 382 mg/dl. IgA deficiency, Low B& T cells, Low Naive cells but no significant infections so far and she was started on prophylactic anibiotics-Septran. VEP and NCV were normal. Prolonged eight hour video EEG monitoring did not reveal any epileptiform abnormalities. No events were recorded. MRI brain was discussed with in house radiologist opined of pure cerebellar atrophy involving both hemispheres.
Both eyes showed dilated episcleral vessels nasally and temporally,
Fundus examination revealed BE disc and macula normal. Dilated and Tortous arteries and veins, opined as probably ocular Telengectasia as there was no other cause for dilated vessels. Genetics consultation was sought, WES was sent and found to be positive for nonsense HET pathogenic (novel), parents are het carriers. parents are carriers for ATM, mother has increased risk upto 25% for breast cancer and 5-10% for pancreatic cancer and 2-3 % risk for ovarian cancer.
And mother was advised mammogram yearly. USG abdomen and pelvis yearly and also advised to bring elder two daughters ( 15 years, 14 years as they have 50% chance to be carriers)
Physiotherapy was initiated.
Dose of phenytoin was down titrated and levipil was continued at prior doses. She was initiated on Tab. Clonazepam.
Overall impression is 6 years old female child with insidious onset progressive dystonia right side upper limb followed lower limbs with ?conjunctival telengiectasia and minimal cerebellar signs.
In view of the elevated AFP and abnormal immunoglobulin levels, the possibility of Ataxia Telangiectasia was considered most likely. She was planned to follow up the child on OPD basis, depending upon the clinical course.
Description:
Ataxia-Telangiectasia (A-T) is a rare and complex genetic disorder that impacts multiple systems in the body. It is caused mutations in the ATM gene, which plays a crucial role in repairing DNA and regulating cell functions. A-T is characterized progressive neurological degeneration (ataxia), dilated blood vessels visible in the skin and eyes (telangiectasia), a weakened immune system, and an increased risk of cancer.
1. Neurological Features (Ataxia):
Progressive Cerebellar Ataxia: Impaired coordination and balance, often beginning in infancy or early childhood, leading to difficulty walking, standing, and fine motor tasks.
Choreoathetosis: Involuntary movements, including twisting or writhing motions.
Oculomotor Apraxia: Difficulty coordinating eye movements, such as shifting gaze between objects.
Speech Difficulties (Dysarthria): Slurred or slow speech due to impaired muscle control.
2. Telangiectasia:
Dilated Blood Vessels: Visible tiny blood vessels on the whites of the eyes (conjunctiva) and areas of the skin such as the face and ears.
Telangiectasia often appears after the onset of ataxia, usually around 3-5 years of age.
3. Immune System Dysfunction:
Frequent Infections: Recurrent respiratory infections due to immunodeficiency, particularly involving low levels of IgA, IgG2, or both.
Increased susceptibility to bacterial and viral infections.
4. Cancer Susceptibility:
Significantly higher risk of cancers, particularly leukemia and lymphoma.
Sensitivity to radiation and DNA-damaging agents increases the cancer risk.
5. Growth and Developmental Delays:
Growth Retardation: Slower growth rates, often resulting in short stature.
Delayed or incomplete puberty due to hormonal imbalances.
6. Sensory and Motor Symptoms:
Dysphagia: Difficulty swallowing, which can lead to choking or aspiration.
Progressive weakness in the limbs.
7. Characteristic Laboratory Findings:
Elevated alpha-fetoprotein (AFP) levels in the blood, a key diagnostic marker.
Chromosomal instability or abnormalities, especially in lymphocytes.
8. Skin and Other Features:
Premature graying of hair.
Café-au-lait spots (in some individuals).
Increased sensitivity to ionizing radiation (X-rays, CT scans).
Genetics: A-T is caused mutations in the ATM (Ataxia Telangiectasia Mutated) gene. The ATM gene is located on chromosome 11q22.3.
Prognosis: The prognosis for individuals with Ataxia-Telangiectasia (A-T) varies depending on the severity of the disease and the management of its complication. Median Life Expectancy is 25 years.
Complications of Ataxia-Telangiectasia (A-T)
Neurological: Progressive ataxia, choreoathetosis, oculomotor apraxia, dysarthria, dysphagia, and peripheral neuropathy.
Immune Deficiency: Recurrent respiratory infections (sinusitis, pneumonia), sepsis risk.
Cancer: Increased risk of leukemia, lymphoma, and solid tumors (e.g., breast cancer).
Respiratory: Chronic lung disease, aspiration pneumonia, bronchiectasis.
Endocrine: Growth retardation, delayed puberty, and risk of diabetes.
Radiation Sensitivity: Complicates imaging and cancer treatments.
Skin and Ocular: Telangiectasia, dry eyes, and conjunctivitis.
Psychological: Depression, anxiety, and social isolation.