PMC6110164_01
Patient 1 (proband) with familial partial lipodystrophy bearing the homozygous p.R582C lamin A mutation at (a,b) age 12 with decompensated hypothyroidism. (c) One year after levothyroxine treatment. Adulthood (d) acanthosis nigricans, (e,f) fat accumulation in the neck and dorsocervical region, and (g,h) loss of subcutaneous tissue in the limbs and abdomen. Morphea hypochromic cutaneous lesions can be seen in the abdomen and trunk.
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F1
The proband (Figure 1) was a 12-year-old girl, born at full-term (birth weight, 3,600 g) as the first child of consanguineous parents, referred to the Universidade Federal do Ceara Clinical Hospital, Fortaleza, Brazil for clinical assessment of short stature and learning disabilities that manifested since age 8.
PMC6110164_02
PMC6110164_03
Patient 2 (proband's sister) with familial partial lipodystrophy bearing the homozygous p.R582C lamin A mutation in adulthood showing loss of subcutaneous tissue in limbs and abdomen, fat accumulation in neck and dorsocervical region, and notable acanthosis nigricans.
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F2
The proband's sister (Figure 2) was born at full-term with a birth weight of 4,800 g.
PMC6110164_04
Patient 3 (proband's mother) bearing the homozygous p.R582C lamin A mutation (a,b) at age 32 showing a phenotype of apparently generalized lipodystrophy without fat accumulation in the neck and face and without acanthosis nigricans. (c) Mother and daughters (from L-R: patients 1, 3, and 2) at ages 19, 32, and 15 years old (L-R).
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F3
When the proband was first examined at our unit, a clinical examination of her mother (Figure 3) at age 32 revealed a severe generalized lipodystrophy phenotype.
PMC6110164_05
Proband's father bearing the heterozygous p.R582C lamin A mutation at age 50 and showing a subtle decrease in subcutaneous fat in the limbs and fat accumulation in the abdomen, without fat accumulation in the neck.
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F4
He is a 50-year-old man with abdominal fat concentration, weighs 72.2 kg, is 170 cm in height, and has a BMI of 24.9 kg/m2 (Figure 4).
Pedigree of the family with lipodystrophy due to the p.R582C lamin A mutation.
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F5
Standard serum determinations are listed in Table 1 and the pedigree of the family is shown in Figure 5.
T1-weighted magnetic resonance imaging of the (1) homozygous proband's sister and (2) the heterozygous father at the levels of (a) orbits and scalp, (b) anterior neck, (c) dorsocervical, (d) thoracolumbar spine, (e) abdomen, (f) pelvis and thighs, (g) knees, and (h) feet. It is worth noting that the sister and father's body mass indices are 20.7 and 24.9 kg/m2, respectively. Note the diffuse absence in subcutaneous tissue of the homozygous proband's sister (indicated by the arrows in a,d-h) and excess fat deposition in the neck and dorsocervical area (indicated by the arrows in b,c).
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F6
Bone marrow fat was markedly reduced in the spine and humerus, relatively preserved in the proximal femur, and normally preserved in the distal femur, tibia, fibula, and feet (Figure 6). Bone marrow fat was also markedly reduced in the spine and humerus (Figure 6).