Seckel syndrome
Seckel syndrome, or microcephalic primordial dwarfism is an extremely rare congenital nanosomic disorder. Inheritance is autosomal recessive. 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, receding mandible and intellectual disability.
A mouse model has been developed. This mouse model is characterized by a severe deficiency of ATR protein. These mice have high levels of replicative stress and DNA damage. Adult Seckel mice display accelerated aging. These findings are consistent with the DNA damage theory of aging.
Symptoms and signs
Symptoms include:- intellectual disability
- microcephaly
- sometimes pancytopenia
- 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 which maps to chromosome 3q22.1–q24. This gene is central in the cell's DNA damage response and repair mechanism.Types include:
| Type | OMIM | Gene | Locus |
| SCKL1 | ATR | 3q23 | |
| SCKL2 | RBBP8 | 18q11 | |
| SCKL4 | CENPJ | 13q12 | |
| SCKL5 | CEP152 | 15q21.1 | |
| SCKL6 | CEP63 | 3q22.2 | |
| SCKL7 | NIN | 14q22.1 | |
| SCKL8 | DNA2 | 10q21.3 | |
| SCKL9 | TRAIP | 3p21.31 | |
| SCKL10 | NSMCE2 | 8q24.13 | |
| SCKL11 | CEP295 | 11q21 |
Diagnosis
There are 4 criteria for diagnosis:- 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
Genetic testing can confirm diagnosis.