There are two main types of FPLD [2]:

• Type I - Loss of fat in the extremities and normal or increased distribution of adipose tissue on the head and neck area, as well as the trunk.
• Type II - Seen only in a few cases, this type is distinguished by loss of fat from both the trunk and the extremities, with marked accumulation in the head and neck region.

Metabolic impairments, primarily in the form of diabetes mellitus, but also hirsutism and dysmenorrhea in women, typically starts during early years of life [3].

The diagnostic workup must comprise a thorough patient history that might reveal a familial presence of symptoms and a thorough physical examination that will identify the distribution of adipose tissue. Laboratory workup reveals hypertriglyceridemia and insulin resistance [3], but because clinical features of this rare genetic syndrome strongly point to an endocrine disease, the diagnosis can be easily missed [2]. For this reason, the role of history taking in these patients is of vital importance.

Management of diabetes mellitus and hyperlipidemia is the mainstay of therapy, whereas leptin replacement therapy is currently under review for use in treating patients with various forms of lipodystrophies [3].

In rare cases, marked hypertriglyceridemia can induce acute pancreatitis and hepatic steatosis, whereas myopathy and cardiomyopathy have been documented as well [3] [5].

Mutations in genes that code for intermediate filaments proteins that serve as constituents of nuclear membranes, known as lamins, are the underlying cause of FPLD [1]. Lamin A and C mutations are transferred by an autosomal dominant pattern of inheritance and the condition is exclusively found in more than one family member [3]. Most recent studies have discovered that mutations in one of the nuclear receptors, the peroxisome proliferator-activated receptor gamma (PPARG), are also associated with the onset of FPLD [4].

FPLD is a very rare condition and only isolated case reports or case series are the sources of data regarding this condition [1] [2] [3] [4] [5]. Neither gender nor ethnic predilection has been established, whereas risk factors are yet to be determined.

Lamins are recognized as essential nuclear membrane proteins and they are coded by Lamin A and C genes [2]. In the setting of mutations, their structure is disrupted and through still unknown mechanisms, individuals suffer from adipose tissue loss and develop a clinical presentation of metabolic syndrome [2] [3].

At this point, prevention strategies against FPLD do not exist.

Familial partial lipodystrophy (FPLD, also known as Köbberling–Dunnigan syndrome), is a rare autosomal dominant genetic disorder that belongs to the group of laminopathies, disorders that are associated with mutations in the lamin A/C gene (LMNA and LMNC, respectively) [1]. The pathogenesis model remains unclear but is thought that mutations in these intermediate filament proteins lead to fat loss and development of insulin resistance [2]. There are two main clinical types: type I, in which fat loss predominantly occurs on the extremities, with normal or slightly increased distribution of adipose tissue in the thorax and the head and neck area; and type II, characterized by loss of fat from both the limbs and the trunk and its accumulation in the neck region [2]. To make the diagnosis, it is necessary to obtain a thorough patient history, perform a detailed physical examination and evaluate serum lipid and glucose levels, as diabetes mellitus and dyslipidemia are frequent findings in these patients [3]. Treatment focuses on managing symptoms, mainly through lipid-lowering drugs and insulin [3].

Familial partial lipodystrophy (FPLD) is a rare genetic disease characterized by loss of fat tissue due to mutations of proteins that serve as building blocks of cell membranes. FPL is transferred by an autosomal dominant pattern of inheritance, meaning that parents will almost certainly transfer the mutated gene to their children and the majority of reported cases involve more than one family member. The disease most frequently presents with loss of fat in the extremities and a normal or somewhat increased amount of fat in the chest and the head and neck area and metabolic diseases such as diabetes mellitus are commonly encountered. Symptoms start in early childhood and the diagnosis can be made by obtaining a detailed patient history that reveals the presence of symptoms in other family members, while blood tests show elevations of triglycerides and glucose. Treatment is currently aimed at controlling diabetes and high lipid levels.

1. Drac H, Madej-Pilarczyk A, Gospodarczyk-Szot K, Gaweł M, Kwieciński H, Hausmanowa-Petrusewicz I. Familial partial lipodystrophy associated with the heterozygous LMNA mutation 1445G>A (Arg482Gln) in a Polish family. Neurol Neurochir Pol. 2010;44(3):291-296.
2. Herbst KL, Tannock LR, Deeb SS, Purnell JQ, Brunzell JD, Chait A. Köbberling type of familial partial lipodystrophy: an underrecognized syndrome. Diabetes Care. 2003 Jun;26(6):1819-1824.
3. Handelsman Y, Oral EA, Bloomgarden ZT, et al. The clinical approach to the detection of lipodystrophyy - An AACE concensus statement. Endocr Pract 2013;19(1):107-116.
4. Demir T, Onay H, Savage DB, Temeloglu E, Uzum AK, Kadioglu P, et al. Familial partial lipodystrophy linked to a novel peroxisome proliferator activator receptor -γ (PPARG) mutation, H449L: a comparison of people with this mutation and those with classic codon 482 Lamin A/C (LMNA) mutations. Diabet Med. 2016;33(10):1445-1450.
5. Jackson SNJ, Howlett TA, McNally PG, O’Rahilly S, Trembath RC. Dunnigan-Kobberling syndrome: an autosomal dominant form of partial lipodystrophy. QJM. 1997;90(1):27-36.