Mixoploidy with a Proteus syndrome phenotype

Abstract

We report a 22-month-old female patient with diploid-triploid mixoploidy (46,XX/69,XXX) and asymmetric overgrowth of the limbs; the legs being more affected, macrodactyly and a subcutaneous lipoma. The patient, A.J., was the 4^th child of a 28-year-old para 3-0-0-3 mother. Family history was unremarkable. Pregnancy was complicated by polyhydramnios in the third trimester and there was small abruptio placentae. Normal spontaneous vertex delivery was at 34 weeks gestation. Apgar scores were 4/8; birth weight was 2280 g (50^th percentile), and OFC was 29 cm (15^th percentile). The large placenta, weight 1310 g, demonstrated triploidy: 69,XXX. Peripheral lymphocyte culture: 21/22 cells were 46,XX and 1 cell was 69,XXX. A higher percentage of mosaicism was present in skin fibroblast culture: 15/6 (46,XX/69,XXX). Recently a macrodactyl toe was removed and cytogenetic studies indicated 3/17 mosaicism (46,XX/69,XXX). Echocardiogram revealed a moderate-sized PDA which closed with Indocin, a trace of tricuspid regurgitation, and moderate pulmonary hypertension. Renal sonogram was normal. At birth, asymmetric macrodactyly of the 2^nd, 3^rd, and 4^th toes and partial 2, 3 toe syndactyly were noted. Palpebral fissures were narrow. At 10.5 months, height was 73.3 cm (60^th percentile), weight was 11.12 kg (above 95^th percentile) and OFC was 46.5 cm (75^th percentile). The lower limbs had grown disproportionately large with increasing asymmetry of all limbs. As a new finding, there was macrodactyly of the 4^th left finger. There was left pes cavovarus. A small subcutaneous lipoma-like mass was present in the right axilla. A developmental assessment at 10.5 months indicated slight motor delay. Due to the limb overgrowth, macrodactyly and subcutaneous lipoma, Proteus syndrome was diagnosed. Somatic mosaicisim has been previously reported with this syndrome, but to our knowledge, this is the first case with mixoploidy; the latter is usually associated with developmental delay, asymmetric growth deficiency (Russell-Silver-like phenotype), cutaneous syndactyly, and facial dysmorphy. Since the mixoploidy may be a causative factor, karyotyping appears warranted for patients with Proteus syndrome.