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 (human)|3] and 18 (human)|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.