View source for Seckel syndrome

{{Infobox medical condition (new)
| name            =
| image           = Bird Headed Dwarf 1.jpg
| caption         = Boy with Seckel syndrome (left)
| field           = [[Medical genetics]]
| synonyms   = Harper's syndrome
| complications   =
| onset           =
| duration        =
| types           =
| causes          = defects of genes on chromosome 3 and 18.
| risks           =
| diagnosis       =
| differential    =
| prevention      =
| treatment       =
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'''Seckel syndrome''', or '''microcephalic [[primordial dwarfism]]''' (also known as '''bird-headed dwarfism''', '''Harper's syndrome''', '''Virchow–Seckel dwarfism''' and '''bird-headed dwarf of Seckel'''<ref name="pmid17921644">{{cite journal |vauthors=Harsha Vardhan BG, Muthu MS, Saraswathi K, Koteeswaran D |title=Bird-headed dwarf of Seckel |journal=J Indian Soc Pedod Prev Dent |volume=25 Suppl |pages=S8–9 |year=2007 |pmid=17921644 |url=http://www.jisppd.com/article.asp?issn=0970-4388;year=2007;volume=25;issue=5;spage=8;epage=9;aulast=Harsha}}</ref>) is an extremely rare [[congenital]] [[dwarfism|nanosomic]] disorder. Inheritance is [[autosomal recessive]].<ref name="WynbrandtLudman2008">{{cite book|author1=James Wynbrandt|author2=Mark D. Ludman|title=The encyclopedia of genetic disorders and birth defects|url=https://books.google.com/books?id=kXaMjwItP0oC&pg=PA344|access-date=7 January 2011|date=February 2008|publisher=Infobase Publishing|isbn=978-0-8160-6396-3|pages=344–}}</ref> 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 fissure]]s,<ref name="PMID29894776">{{cite journal |vauthors=Jung M, Rai A, Wang L, Puttmann K, Kukreja K, Koh CJ |title=Nephrolithiasis in a 17-Year-Old Male With Seckel Syndrome and Horseshoe Kidneys: Case Report and Review of the Literature |journal= Urology |volume= 120|pages=241–243 |pmid=29894776 |doi=10.1016/j.urology.2018.05.023 |year=2018 |s2cid=48353132 }}</ref> receding [[Human mandible|mandible]] and [[intellectual disability]].

A mouse model has been developed.<ref name="pmid19620979">{{cite journal  |vauthors=Murga M, Bunting S, Montaña MF, etal |title=A mouse model of ATR-Seckel shows embryonic replicative stress and accelerated aging|journal=Nat. Genet. |volume=41 |issue=8 |pages=891–8 |date=August 2009 |pmid=19620979 |pmc=2902278 |doi=10.1038/ng.420 }}</ref> This mouse model is characterized by a severe deficiency of [[Ataxia telangiectasia and Rad3 related|ATR]] protein.<ref name="pmid19620979" /> These mice have high levels of replicative stress and [[DNA damage (naturally occurring)|DNA damage]]. Adult Seckel mice display accelerated aging.<ref name="pmid19620979" /> These findings are consistent with the [[DNA damage theory of aging]].

== Symptoms and signs ==
Symptoms include:<ref name=":0">{{Cite web |title=Seckel Syndrome - Symptoms, Causes, Treatment {{!}} NORD |url=https://rarediseases.org/rare-diseases/seckel-syndrome/ |access-date=2025-01-10 |website=rarediseases.org |language=en-US}}</ref>
* [[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]] [[Chromosome 3 (human)|3]] and [[Chromosome 18 (human)|18]]. One form of Seckel syndrome can be caused by mutation in the gene encoding the [[ataxia telangiectasia and Rad3 related|ataxia telangiectasia and Rad3-related]] protein ({{Gene|ATR}}) which maps to chromosome 3q22.1–q24. This gene is central in the cell's DNA damage response and repair mechanism.

Types include:<ref>{{Cite web |title=Entry - #210600 - SECKEL SYNDROME 1; SCKL1 - OMIM |url=https://omim.org/entry/210600 |access-date=2025-01-10 |website=omim.org |language=en-us}}</ref>
{| class="wikitable"
|-
! Type
! [[OMIM]]
! Gene
! Locus
|-
| SCKL1
| {{OMIM|210600||none}}
| ''[[Ataxia telangiectasia and Rad3 related|ATR]]''
| 3q23
|-
| SCKL2
| {{OMIM|606744||none}}
| [[RBBP8]]
| 18q11
|-
| SCKL4
| {{OMIM|613676||none}}
| ''[[CENPJ]]''
| 13q12
|-
|SCKL5
|[https://omim.org/entry/613823 613823]
|[[CEP152]]
|15q21.1
|-
|SCKL6
|[https://omim.org/entry/614728 614728]
|[[CEP63]]
|3q22.2
|-
|SCKL7
|[https://omim.org/entry/614851 614851]
|[[NIN (gene)|NIN]]
|14q22.1
|-
|SCKL8
|[https://omim.org/entry/615807 615807]
|[[DNA2L|DNA2]]
|10q21.3
|-
|SCKL9
|[https://omim.org/entry/616777 616777]
|[[TRAF interacting protein|TRAIP]]
|3p21.31
|-
|SCKL10
|[https://omim.org/entry/617253 617253]
|[[NSMCE2]]
|8q24.13
|-
|SCKL11
|[https://omim.org/entry/620767 620767]
|[[CEP295]]
|11q21
|}

==Diagnosis==
There are 4 criteria for diagnosis:<ref>{{Citation |last1=Bissonnette |first1=Bruno |title=Seckel Syndrome |date=2019 |work=Syndromes: Rapid Recognition and Perioperative Implications |url=https://accesspediatrics.mhmedical.com/content.aspx?bookid=2674&sectionid=220544462#:~:text=Four%20criteria%20are%20diagnostic:%20(1,of%20the%20corpus%20callosum,%20dysgenetic |access-date=2025-01-10 |edition=2 |place=New York, NY |publisher=McGraw-Hill Education |last2=Luginbuehl |first2=Igor |last3=Engelhardt |first3=Thomas}}</ref>

# 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.<ref>{{Citation |last1=Bissonnette |first1=Bruno |title=Seckel Syndrome |date=2019 |work=Syndromes: Rapid Recognition and Perioperative Implications |url=https://accesspediatrics.mhmedical.com/content.aspx?bookid=2674&sectionid=220544462#:~:text=Four%20criteria%20are%20diagnostic:%20(1,of%20the%20corpus%20callosum,%20dysgenetic |access-date=2025-01-10 |edition=2 |place=New York, NY |publisher=McGraw-Hill Education |last2=Luginbuehl |first2=Igor |last3=Engelhardt |first3=Thomas}}</ref>

Genetic testing can confirm diagnosis.<ref name=":0" />

== Treatment ==
There is no cure for Seckel syndrome. Symptomatic treatment is available.<ref>{{Cite web |title=Seckel Syndrome - Symptoms, Causes, Treatment {{!}} NORD |url=https://rarediseases.org/rare-diseases/seckel-syndrome/#therapies |access-date=2025-01-10 |website=rarediseases.org |language=en-US}}</ref><ref>{{Cite journal |last1=Kelana |first1=Andreas Dhymas Dhyna Martha |last2=Windiani |first2=Gusti Ayu Trisna |last3=Arimbawa |first3=Made |last4=Adnyana |first4=Gusti Agung Ngurah Sugitha |last5=Yuda |first5=Made Darma |last6=Murti |first6=Ni Luh Sukma Pratiwi |last7=Soetjiningsih |first7=Soetjiningsih |date=2023-01-04 |title=Case of Seckel Syndrome in a 9-month-old Girl |url=https://oamjms.eu/index.php/mjms/article/view/10988 |journal=Open Access Macedonian Journal of Medical Sciences |language=en |volume=11 |issue=C |pages=6–10 |doi=10.3889/oamjms.2023.10988 |issn=1857-9655|doi-access=free }}</ref>

== History ==
The syndrome was named after German–American physician [[Helmut Paul George Seckel]]<ref>Seckel, H. P. G. Bird-headed Dwarfs: Studies in Developmental Anthropology Including Human Proportions.  Springfield, Ill.: Charles C Thomas (pub.) 1960.</ref> (1900–1960). The synonym Harper's syndrome was named after pediatrician [[Rita G. Harper]].<ref>{{Cite web |title=Seckel's syndrome |url=http://www.whonamedit.com/synd.cfm/869.html}}</ref><ref name="pmid6022184">{{cite journal |vauthors=Harper RG, Orti E, Baker RK |date=May 1967 |title=Bird-beaded dwarfs (Seckel's syndrome). A familial pattern of developmental, dental, skeletal, genital, and central nervous system anomalies |journal=J. Pediatr. |volume=70 |issue=5 |pages=799–804 |doi=10.1016/S0022-3476(67)80334-2 |pmid=6022184}}</ref>

== See also ==
* [[Koo-Koo the Bird Girl]]

== References ==
{{reflist}}

== External links ==
* {{WhoNamedIt|synd|869|Seckel's syndrome}}
{{Medical resources
|   DiseasesDB     = 31625
|   ICD10          = {{ICD10|Q|87|1|q|80}}
|   ICD9           ={{ICD9|759.89}}
|   ICDO           =
|   OMIM           = 210600
|   MedlinePlus    =
|   eMedicineSubj  =
|   eMedicineTopic =
| MeSH=C537533
| Orphanet=808
}}

{{Phakomatoses and other congenital malformations not elsewhere classified}}
{{Deficiencies of intracellular signaling peptides and proteins}}
{{Nucleus diseases}}

[[Category:Congenital disorders]]
[[Category:Growth disorders]]
[[Category:Syndromes with microcephaly]]
[[Category:Syndromes affecting stature]]
[[Category:Syndromes with intellectual disability]]
[[Category:Rare syndromes]]