Seckel syndrome
Template:Infobox medical condition (new) Seckel syndrome, or microcephalic primordial dwarfism (also known as bird-headed dwarfism, Harper's syndrome, Virchow–Seckel dwarfism and bird-headed dwarf of Seckel[1]) is an extremely rare congenital nanosomic disorder. Inheritance is autosomal recessive.[2] It is characterized by intrauterine growth restriction and postnatal dwarfism with a small head, narrow bird-like face with a beak-like nose, large eyes with down-slanting palpebral fissures,[3] receding mandible and intellectual disability.
A mouse model has been developed.[4] This mouse model is characterized by a severe deficiency of ATR protein.[4] These mice have high levels of replicative stress and DNA damage. Adult Seckel mice display accelerated aging.[4] These findings are consistent with the DNA damage theory of aging.
Symptoms and signs
Symptoms include:[5]
- intellectual disability (more than half of the patients have an IQ below 50)
- microcephaly
- sometimes pancytopenia (low blood counts)
- cryptorchidism in males
- low birth weight
- dislocations of pelvis and elbow
- unusually large eyes
- blindness or visual impairment
- large, low-set ears
- small chin due to receded lower jaw
Genetics
It is believed to be caused by defects of genes on chromosome 3 and 18. One form of Seckel syndrome can be caused by mutation in the gene encoding the ataxia telangiectasia and Rad3-related protein (ATR) which maps to chromosome 3q22.1–q24. This gene is central in the cell's DNA damage response and repair mechanism.
Types include:[6]
| Type | OMIM | Gene | Locus |
|---|---|---|---|
| SCKL1 | 210600 | ATR | 3q23 |
| SCKL2 | 606744 | RBBP8 | 18q11 |
| SCKL4 | 613676 | CENPJ | 13q12 |
| SCKL5 | 613823 | CEP152 | 15q21.1 |
| SCKL6 | 614728 | CEP63 | 3q22.2 |
| SCKL7 | 614851 | NIN | 14q22.1 |
| SCKL8 | 615807 | DNA2 | 10q21.3 |
| SCKL9 | 616777 | TRAIP | 3p21.31 |
| SCKL10 | 617253 | NSMCE2 | 8q24.13 |
| SCKL11 | 620767 | CEP295 | 11q21 |
Diagnosis
There are 4 criteria for diagnosis:[7]
- Congenital Dwarfism and postnatal growth retardation
- Microcephaly, large eyes, beak-like nose, narrow face, retrognathism, malocclusion
- Mental handicap
- Agenesis of the corpus callosum, cerebral cysts
Other abnormalities can be a supportive criteria, such as: anemia, pancytopenia, cleft lip/palate scoliosis or kyphoscoliosis.[8]
Genetic testing can confirm diagnosis.[5]
Treatment
There is no cure for Seckel syndrome. Symptomatic treatment is available.[9][10]
History
The syndrome was named after German–American physician Helmut Paul George Seckel[11] (1900–1960). The synonym Harper's syndrome was named after pediatrician Rita G. Harper.[12][13]
See also
References
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- ↑ Seckel, H. P. G. Bird-headed Dwarfs: Studies in Developmental Anthropology Including Human Proportions. Springfield, Ill.: Charles C Thomas (pub.) 1960.
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External links
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