Lipodystrophy: an unusual diagnosis in a case of oligomenorrhea and hirsutism

Abstract

Background: Familial partial lipodystrophy, Dunnigan variety, is a rare autosomal dominant disorder caused by missense mutations in LMNA gene. Individuals are predisposed to insulin resistance and its complications, including features of polycystic ovary syndrome.

Case: A 27-year-old Hispanic woman presented with oligomenorrhea and hirsutism. Examination revealed cushingoid facies, significant hirsutism, acanthosis nigricans, and a lean body habitus. Metabolic testing identified diabetes mellitus, dyslipidemia, and steatohepatitis. A diagnosis of familial partial lipodystrophy, Dunnigan variety, was confirmed by the detection of a heterozygous p.Arg482Trp (c.1444C>T) missense mutation in the lamin A/C (LMNA) gene. Subsequently, seven female relatives were diagnosed with familial partial lipodystrophy, Dunnigan variety, four of whom had menstrual irregularities.

Conclusion: Familial partial lipodystrophy, Dunnigan variety, can present with features similar to polycystic ovary syndrome. Diagnosis is critical because the metabolic complications of the disorder have significant morbidity.

Figure 1

(A and B): Anterior and lateral views of the index patient showing marked loss of subcutaneous fat from the extremities, hips and anterior abdomen, with excess fat deposition around the face, and in the submental and dorsocervical regions. Also note the presence of acanthosis nigricans over the neck, poor breast development, and increased vulvar fat. (C): FPLD Pedigree with patient numbers corresponding to data in Table 1. Affected individuals are shown as filled black symbols, unaffected subjects as unfilled symbols, and deceased individuals are indicated by a diagonal line. Squares represent males and circles represent females. Arrow indicates the index subject. RR indicates a subject with the normal LMNA genotype (Arginine in position 482 for both alleles), while RW indicates patients with the heterozygous missense LMNA mutation (Arginine and Tryptophan in position 482). (D) Sequence electropherogram of LMNA exon 8, with arrow showing the site of heterozygous missense mutation, c.1444C>T, resulting in substitution of one of the normal alleles, Arginine by Tryptophan at position 482. The colors denote nucleic acids; blue=cytosine (C), green=adenine (A), red=thymine (T), black=guanine (G). N, possible missense mutation.

Figure 1

(A and B): Anterior and lateral views of the index patient showing marked loss of subcutaneous fat from the extremities, hips and anterior abdomen, with excess fat deposition around the face, and in the submental and dorsocervical regions. Also note the presence of acanthosis nigricans over the neck, poor breast development, and increased vulvar fat. (C): FPLD Pedigree with patient numbers corresponding to data in Table 1. Affected individuals are shown as filled black symbols, unaffected subjects as unfilled symbols, and deceased individuals are indicated by a diagonal line. Squares represent males and circles represent females. Arrow indicates the index subject. RR indicates a subject with the normal LMNA genotype (Arginine in position 482 for both alleles), while RW indicates patients with the heterozygous missense LMNA mutation (Arginine and Tryptophan in position 482). (D) Sequence electropherogram of LMNA exon 8, with arrow showing the site of heterozygous missense mutation, c.1444C>T, resulting in substitution of one of the normal alleles, Arginine by Tryptophan at position 482. The colors denote nucleic acids; blue=cytosine (C), green=adenine (A), red=thymine (T), black=guanine (G). N, possible missense mutation.

Figure 1

(A and B): Anterior and lateral views of the index patient showing marked loss of subcutaneous fat from the extremities, hips and anterior abdomen, with excess fat deposition around the face, and in the submental and dorsocervical regions. Also note the presence of acanthosis nigricans over the neck, poor breast development, and increased vulvar fat. (C): FPLD Pedigree with patient numbers corresponding to data in Table 1. Affected individuals are shown as filled black symbols, unaffected subjects as unfilled symbols, and deceased individuals are indicated by a diagonal line. Squares represent males and circles represent females. Arrow indicates the index subject. RR indicates a subject with the normal LMNA genotype (Arginine in position 482 for both alleles), while RW indicates patients with the heterozygous missense LMNA mutation (Arginine and Tryptophan in position 482). (D) Sequence electropherogram of LMNA exon 8, with arrow showing the site of heterozygous missense mutation, c.1444C>T, resulting in substitution of one of the normal alleles, Arginine by Tryptophan at position 482. The colors denote nucleic acids; blue=cytosine (C), green=adenine (A), red=thymine (T), black=guanine (G). N, possible missense mutation.

Figure 2

T1 weighted magnetic resonance images of the head and neck, abdomen and thigh from the index patient (A, C and E, respectively) and a normal 25-year old female subject (B, D and F, respectively). Compared to the normal subject, patient has increased fat in the dorsocervical, submental and intra-abdominal regions (as shown by arrows), but marked paucity of subcutaneous fat in the thigh and anterior abdomen.