View source for Medicine:Familial partial lipodystrophy

{{Infobox medical condition (new)
| name            = Familial partial lipodystrophy
| synonyms        = FPLD<ref>{{cite web |title=Orphanet: Familial partial lipodystrophy |url=https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=98306 |website=www.orpha.net |access-date=27 April 2019 |language=en}}</ref>
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'''Familial partial lipodystrophy''', also known as '''Köbberling–Dunnigan syndrome''',<ref name="Bolognia">{{cite book |author=Rapini, Ronald P. |author2=Bolognia, Jean L. |author3=Jorizzo, Joseph L. |title=Dermatology: 2-Volume Set |publisher=Mosby |location=St. Louis |year=2007 |pages=1541–2, 1543 |isbn=978-1-4160-2999-1 }}</ref> is a rare genetic metabolic condition characterized by the loss of subcutaneous fat.<ref name="Andrews">{{cite book |author=James, William D. |author2=Berger, Timothy G.|title=Andrews' Diseases of the Skin: clinical Dermatology |publisher=Saunders Elsevier |year=2006 |isbn=978-0-7216-2921-6 |display-authors=0}}</ref>{{rp|495}}

FPL also refers to a rare metabolic condition in which there is a loss of subcutaneous fat in the arms, legs and lower torso. The upper section of the body, face, neck, shoulders, back and trunk carry an excess amount of fat.

As the body is unable to store fat correctly this leads to fat around all the vital organs and in the blood (triglycerides). This results in heart problems, cirrhosis of the liver, lipoatrophic diabetes, and pancreatitis, along with various other complications.

==Types==
{| class="wikitable"
|-
! OMIM
! Name
! Locus
|-
| {{OMIM|608600||none}}
| FPLD1 (Kobberling-type, loss from extremities)
| ?
|-
| {{OMIM|151660||none}}
| FPLD2	([[Medicine:Dunnigan familial partial lipodystrophy|Dunnigan-type]], loss from limbs and trunk)
| [[Biology:LMNA|LMNA]]; 1q21.2
|-
| {{OMIM|604367||none}}
| FPLD3
| PPARG; 7q11.23-q21.11, 3p25
|}

==Presentation ==

Type 1 is believed to be underdiagnosed.<ref name="pmid12766116">{{cite journal |vauthors=Herbst KL, Tannock LR, Deeb SS, Purnell JQ, Brunzell JD, Chait A |title=Köbberling type of familial partial lipodystrophy: an underrecognized syndrome |journal=Diabetes Care |volume=26 |issue=6 |pages=1819–24 |date=June 2003 |pmid=12766116 |doi= 10.2337/diacare.26.6.1819|url=http://care.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=12766116|doi-access=free }}</ref>

==Genetics==

A mutations in a number of genes have been associated with this condition. [[Biology:Mutation|Mutation]]s associated with FPL have been reported in ''[[Biology:LMNA|LMNA]]'' (lamin A/C), ''PPARG'' (PPARγ), ''[[Biology:AKT2|AKT2]]'' (AKT serine/threonine kinase 2), ''PLIN1'' (perilipin-1), and ''CIDEC'' (cell-death-inducing DFFA-like effector B).<ref name="pmid21865368">{{cite journal | vauthors = Garg A | title = Clinical review#: Lipodystrophies: genetic and acquired body fat disorders | journal = J. Clin. Endocrinol. Metab. | volume = 96 | issue = 11 | pages = 3313–25 | year = 2011 | pmid = 21865368 | doi = 10.1210/jc.2011-1159 | pmc = 7673254 | doi-access = free }}</ref>

Six types (1-6) have been described. Types 1-5 are inherited in an autosomal dominant fashion.

Type 1 (Kobberling variety, FPL1) is very rare and has only been reported in women to date. Fat loss is confined to the limbs and mostly in the distal parts. Central obesity may be present. Complications include hypertension, insulin resistance and hypertriglyceridemia. The gene causing this condition is not yet known. This form was first described in 1975.

Type 2 (Dunnigan Variety, FPL2) is the most common form and is due to mutations in the [[Biology:LMNA|LMNA]] gene. Over 500 cases have been reported to date. Development up to puberty is normal. Fat is then gradually lost in is the limbs and trunk. Fat may accumulate around the face and between the shoulder blades. Insulin resistance is common. Other conditions associated with this condition include [[Medicine:Acanthosis nigricans|acanthosis nigricans]], fatty liver, hypertriglyceridemia and [[Medicine:Polycystic ovary syndrome|polycystic ovary syndrome]] in women. There is an increased risk of coronary heart disease. [[Medicine:Cardiomyopathy|Cardiomyopathy]] and muscular dystrophy may occur rarely. [[Medicine:Xanthoma|Xanthoma]] and nail changes may occur.

Type 3 is due to mutations in the PPARG gene. It is rare with approximately 30 cases reported to date. It is similar to type 2 but tends to be milder.

Type 4 is due to mutations in the PLIN1 gene. It is rare with only a small number of cases reported. Fat loss tends to affect the lower limbs and buttocks. Insulin resistance and hypertriglyceridemia occur. Calf muscular hypertrophy may occur.

Type 5 is due to mutations in the [[Biology:AKT2|AKT2]] gene. It has been reported in four patients all members of the same family. Fat loss affects the upper and lower limbs. The patients also had hypertension, insulin resistance and hypertriglyceridemia.

Type 6 due to mutations in the  CIDEC gene. It is inherited in an autosomal recessive fashion and has been reported in only one patient to date. Features included  fat loss, severe insulin resistance, fatty liver, acanthosis nigricans and diabetes.

Another gene that has been associated with this condition is AGPAT2.<ref name=Broekema2018>Broekema MF, Massink MPG, De Ligt J, Stigter ECA, Monajemi H, De Ridder J, Burgering BMT, van Haaften GW, Kalkhoven E (2018) A single complex Agpat2 allele in a patient With partial lipodystrophy. Front Physiol 9:1363. doi: 10.3389/fphys.2018.01363.</ref>

==Diagnosis==

==Treatment==

==Prevalence==

This not known with certainty but is estimated to be about one per million. It appears to be more common in females than males.

== See also ==
* Lipodystrophy
* List of cutaneous conditions

== References ==
{{reflist}}

== External links ==
{{Medical resources
|  ICD10           = E88.1
|  ICD9            = <!--{{ICD9|xxx}}-->
|  ICDO            = 
|  OMIM            = 608600
|  DiseasesDB      = 
|  MedlinePlus     = 
|  eMedicineSubj   = 
|  eMedicineTopic  = 
|  MeSH            = D052496
|  GeneReviewsNBK  = 
|  GeneReviewsName = 
|  Orphanet        = 98306
}}
{{Transcription factor/coregulator deficiencies}}

[[Category:Syndromes]]

{{Sourceattribution|Familial partial lipodystrophy}}