Localized gigantism: Macrodystrophia lipomatosa

By Nikki Elmi

Macrodystrophia Lipomatosa (MDL) is a rare congenital overgrowth disorder characterized by an excessive and disproportionate growth of one or more digits (fingers or toes), and sometimes an entire limb. The overgrowth involves not just adipose (fat) tissue but also other mesenchymal components; bone, nerves, connective tissue, possibly muscles and periosteum. Typically present from birth or early childhood, the disorder often becomes more prominent as the child grows. The enlarged parts can result in cosmetic, functional, and sometimes neurological problems, especially if nerves are compressed.

Though the precise cause of MDL remains incompletely understood, several overlapping theories and findings have emerged. One major line of evidence suggests that there are genetic contributions, including somatic mutations (acquired in the embryo or fetus) in growth regulatory pathways. These could dysregulate cell proliferation, adipose tissue growth, and possibly lead to local overactivation of signaling cascades such as the PI3K/AKT pathway. Other proposed etiologic mechanisms include disturbances in fetal circulation, segmentation errors during embryologic limb development, lipomatous degeneration, and imbalance in growth inhibiting versus growth promoting factors.

In MDL, fibroadipose tissue proliferates excessively, infiltrating the dermal connective tissue and subcutaneous spaces; there may also be involvement of nerve sheaths (fibrolipomatous hamartomas), muscles, periosteum, and even bone marrow. The bone components (phalanges, metacarpals/metatarsals) often show hypertrophy, widening, thickening, splaying, and sometimes exostoses. Enlargement progresses through childhood and often stabilizes after skeletal maturity. Because of the involvement of nerves and sometimes joint or skeletal structure, functional issues like impaired motion, deformity, or neurologic symptoms can develop.

Diagnosis of MDL is multimodal, depending on clinical, radiologic, and histopathologic findings. Clinically, one sees disproportionate enlargement of digits or limb segments (often following a particular nerve distribution, e.g. median nerve in the hand or the plantar nerves in the foot), sometimes with deformity and functional impairment. Radiographic imaging begins with plain X-rays: these show enlargement of soft tissues, hypertrophy of bones (increased length and diameter), cortical thickening, widened phalanges, possibly bone deformity. MRI is especially useful, showing characteristic fibroadipose overgrowth with signal intensity similar to normal fat on T1- and T2-weighted images; it helps delineate the extent, involvement of deeper tissues, nerve sheaths, and relation to muscles and tendons. Ultrasound or Doppler imaging may help exclude vascular malformations.

Histopathologic confirmation shows abundant adipose tissue interwoven with fibrous septa, infiltration of connective tissue, sometimes involvement of nerve substance and other mesenchymal components.

As for treatment, there is no cure; management is surgical and symptomatic. The goals are preserving function, reducing deformity, improving appearance, and alleviating discomfort. Soft-tissue debulking (removal of excess fibrofatty tissue), bone reshaping or resection (osteotomies), and, in extreme deformities, partial or total amputation or ray resection are surgical options. Timing of surgery is important; many surgeons delay definitive surgery until growth slows or is complete, unless there are severe functional or neurological impairments. Multiple staged surgical procedures are common. Risks include recurrence of overgrowth (reported in many cases), nerve injury (especially in more aggressive debulking), wound healing complications, sensory loss, and in some cases need for further surgeries. Postoperative outcomes can include improved function (e.g. grasping, walking) and better cosmetic appearance, though sometimes with residual deficits.

Histopathologic finding shows an overgrowth of fatty tissue within the fibrous tissue and the substance of the nerve

Macrodystrophia Lipomatosa remains a difficult condition to manage. While the overgrowth is benign (non‐malignant), its impact can be substantial; physical deformities, functional impairment, psychosocial burden. Current therapies are largely surgical and largely palliative, with significant risk of recurrence and complications. Early diagnosis helps with planning, but there are many unanswered questions about optimal timing, techniques, and long‐term outcomes.

Future research needs to focus on several areas: deeper understanding of the molecular and genetic underpinnings (e.g. identifying specific mutations, signaling pathways, growth factor dysregulation) to possibly open doors for medical or targeted therapies; rigorous longitudinal studies tracking patients over many years to establish best surgical timing, standardize procedures, and measure functional, cosmetic, neurological, and quality-of-life outcomes; refinement of imaging and diagnostics that help predict which cases will progress severely, or which surgical approach will yield best results; and exploring non‐surgical adjuncts (like molecular inhibitors or therapies) to reduce recurrence or slow progression. With better basic science insights plus careful clinical trial and multi‐center collaboration, the hope is that management will become more predictable, safer, and more effective, not just ameliorating symptoms, but altering disease course.

By Nikki Elmi

References:

Bodard, S., Guinebert, S., Kastler, B., et al. (2022). Bilateral macrodystrophia lipomatosa hand with fibrolipohamartoma of median and ulnar nerve. Clinical Images & Case Reports Journal, 4(1). Retrieved from https://www.literaturepublishers.org/archive/Bilateral-Macrodystrophia-Lipomatosa-Hand-with-Fibrolipohamartoma-of-Median-and-Ulnar-Nerve.html

Goldman, A. B., & Kaye, J. J. (1977). Macrodystrophia lipomatosa: Radiographic diagnosis. American Journal of Roentgenology, 128(1), 101–105. Retrieved from https://www.ajronline.org/doi/epdf/10.2214/ajr.128.1.101

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Taruna Yadav, Mirza, G., Khera, P. S., & Garg, P. (2020). Macrodystrophia lipomatosa with fibrolipomatous hamartoma of medial plantar nerve and lipomatosis of thigh. Sudan Journal of Paediatrics, 20(1), 62–67. Retrieved from https://pmc.ncbi.nlm.nih.gov/articles/PMC3665877/

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