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Alpha-thalassemia-intellectual disability syndrome linked to chromosome 16
Disease definition
A rare developmental defect during embryogenesis, a contiguous gene deletion syndrome, is a form of alpha-thalassemia characterized by microcytosis, hypochromia, normal hemoglobin (Hb) level or mild anemia, associated with developmental abnormalities.
ORPHA:98791
Classification level: Disorder- Synonym(s):
- ATR syndrome linked to chromosome 16
- ATR syndrome, deletion type
- ATR-16 syndrome
- Alpha thalassemia-intellectual disability syndrome, deletion type
- Prevalence: <1 / 1 000 000
- Inheritance: Not applicable or Unknown
- Age of onset: Infancy, Neonatal
- ICD-10: D56.0
- ICD-11: 3A50.1
- OMIM: 141750
- UMLS: C0795917
- MeSH: C563050
- GARD: -
- MedDRA: -
Summary
Epidemiology
Alpha-thalassemia-intellectual disability syndrome linked to chromosome 16 (ATR-16) prevalence is unknown. More than 20 cases have been reported to date.
Clinical description
ATR-16 is a congenital disease. Patients present with either alpha-thalassemia trait or mild hemoglobin H disease (HbH disease) associated with a mild to profound (in most cases) intellectual disability and, in some cases, with mild, nonspecific dysmorphic features (mild hypertelorism, down slanted palpebral fissures, broad or prominent nasal bridge, small ears, short neck), microcephaly and short stature. Genital abnormalities (hypospadias and cryptorchidism) have been reported in males. Club foot is common.
Etiology
ATR-16 is due to large deletions on chromosome band 16p13.3 which remove the alpha-globin genes (HBA1 and HBA2), and many other flanking genes. The gene(s) responsible for intellectual deficiency and other developmental abnormalities has not been clearly identified. All cases are due to de novo deletions or segregation for parental translocations inherited in an unbalanced manner.
Diagnostic methods
Diagnosis is based on the clinical picture and confirmed by cytogenetic testing. Routine cytogenetic studies may be sufficient to identify the deletion. However, in some instances other methods such as comparative genomic hybridization (CGH) arrays are used to detect cryptic subtelomeric deletions.
Differential diagnosis
Differential diagnosis includes Alpha thalassemia - X-linked intellectual deficit syndrome, and the co-occurrence of common alpha-thalassemia trait and an intellectual deficiency of another cause.
Antenatal diagnosis
Antenatal diagnosis is indicated in cases of parental translocations but it can also be offered to parents of a patient with de novo deletions to prevent recurrence due to germline mosaicism.
Genetic counseling
Genetic counseling is possible when parents are known carriers of the chromosomal translocation.
Management and treatment
There is no treatment for ATR-16. Management is symptom-based and requires a multidisciplinary approach. Management of intellectual deficiency usually includes speech therapy and individualized educational plans. In case of anemia, specific treatment may include occasional red blood cell transfusions, iron chelation and other supportive measures.
Prognosis
The prognosis is highly variable, depending on the degree of intellectual deficiency.
A summary on this disease is available in Deutsch (2020) Español (2020) Italiano (2020) Nederlands (2020) Français (2013) Português (2013) Polski (2013, pdf)
Detailed information
Guidelines
- Clinical practice guidelines
- English (2010) - Br J Haematol
- English (2015) - Eur J Hum Genet
Genetic Testing
- Guidance for genetic testing
- Français (2019, pdf) - ANPGM
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