Macrodactyly in tuberous sclerosis complex: Case report and review of the literature

Abstract

Macrodactyly in the context of tuberous sclerosis complex (TSC) is a known but rare manifestation. We report the case of a boy diagnosed with TSC at 2 years and 4 months of age, presenting with bilateral macrodactyly of the first three fingers of both hands, with underlying radiographic changes, in whom molecular analysis identified a frameshift mutation on the TSC1 gene (encoding hamartin), leading to a premature stop codon. We reviewed the literature for reported cases of TSC patients with the same manifestation. In four of 14 patients, including ours, macrodactyly caused some type of joint limitation or flexion deformity, thus contradicting the established idea that this is a finding without clinical significance. Our patient is, to our knowledge, the first reported to have clear bilateral involvement. We briefly discuss the underlying mechanism for this phenomenon, which has yet to be fully elucidated, although somatic mosaicism for loss of heterozygosity at TSC loci is a plausible explanation. © 2016 Wiley Periodicals, Inc.

Somatic overgrowth disorders of the PI3K/AKT/mTOR pathway & therapeutic strategies

“…Those who may have type 2 mosaicism include those who have TSC plus features similar to the overgrowth syndromes discussed earlier. For example, there are individuals with TSC who also have unilateral or bilateral overgrowth of digits, hand, or an extremity [Soeiro E Sá et al, ] (Fig. ).…”

Macrodactyly in tuberous sclerosis complex

“…Macrodactyly in TSC appears to be on the spectrum of similar hamartomas. It has also been reported in other neurocutaneous syndromes such as Proteus syndrome, neurofibromatosis type 1, Sturge–Weber syndrome and Klippel–Trenaunay syndrome 1,4 …”

“…Macrodactyly is a rare, and perhaps under‐recognized, manifestation of TSC 1 . It usually presents as a unilateral enlargement of one or few fingers, generally affecting the first, second or third digits.…”

“…Histopathology shows thickened collagen bundles or fibrocollagenous tissue, suggestive of a collagenoma or fibrous hamartoma, respectively. Underlying bone changes are common, and include increase in bone width, periosteal reaction, irregular cortical thickening, erosive lesions and cortical cysts 1 . The mechanism for such a localized tissue hyperplasia is not completely understood, but somatic mosaicism for loss of heterozygosity at one or more of the TSC loci has been proposed 2 .…”

Limb overgrowth associated with a mosaic TSC2 second‐hit in tuberous sclerosis complex

“…We read with great interest the article "Macrodactyly in tuberous sclerosis complex: Case report and review of the literature" by Soeiro e Sá, Moldovan, and Sousa (2016). They report on a boy diagnosed with tuberous sclerosis complex (TSC), presenting with bilateral macrodactyly of the first three fingers of both hands, harboring a frameshift variant of the TSC1 gene on blood samples.…”