Seckel syndrome

Seckel syndrome
Other names	Harper's syndrome
Boy with Seckel syndrome (left)
Specialty	Medical genetics
Causes	defects of genes on chromosome 3 and 18.

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:^{[citation needed]}

• 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:

Type	OMIM	Gene	Locus
SCKL1	210600	ATR	3q22–q24
SCKL2	606744	?	18p11–q11
SCKL3	608664	?	14q
SCKL4	613676	CENPJ	13q12

Diagnosis

Treatment

History

The syndrome was named after German–American physician Helmut Paul George Seckel^[5] (1900–1960). The synonym Harper's syndrome was named after pediatrician Rita G. Harper.^[6][7]

See also

• Koo-Koo the Bird Girl

References

1. Harsha Vardhan BG, Muthu MS, Saraswathi K, Koteeswaran D (2007). "Bird-headed dwarf of Seckel". J Indian Soc Pedod Prev Dent. 25 Suppl: S8–9. PMID 17921644.
2. James Wynbrandt; Mark D. Ludman (February 2008). The encyclopedia of genetic disorders and birth defects. Infobase Publishing. pp. 344–. ISBN 978-0-8160-6396-3. Retrieved 7 January 2011.
3. Jung M, Rai A, Wang L, Puttmann K, Kukreja K, Koh CJ (2018). "Nephrolithiasis in a 17-Year-Old Male With Seckel Syndrome and Horseshoe Kidneys: Case Report and Review of the Literature". Urology. 120: 241–243. doi:10.1016/j.urology.2018.05.023. PMID 29894776. S2CID 48353132.
4. Murga M, Bunting S, Montaña MF, et al. (August 2009). "A mouse model of ATR-Seckel shows embryonic replicative stress and accelerated aging". Nat. Genet. 41 (8): 891–8. doi:10.1038/ng.420. PMC 2902278. PMID 19620979.
5. Seckel, H. P. G. Bird-headed Dwarfs: Studies in Developmental Anthropology Including Human Proportions. Springfield, Ill.: Charles C Thomas (pub.) 1960.
6. "Seckel's syndrome".
7. Harper RG, Orti E, Baker RK (May 1967). "Bird-beaded dwarfs (Seckel's syndrome). A familial pattern of developmental, dental, skeletal, genital, and central nervous system anomalies". J. Pediatr. 70 (5): 799–804. doi:10.1016/S0022-3476(67)80334-2. PMID 6022184.

External links

• Seckel's syndrome at Who Named It?