Plantar lipomatosis, unusual facies, and developmental delay: Confirmation of Pierpont syndrome

Abstract

In 1998, Pierpont et al. reported on two unrelated boys with plantar lipomatosis, unusual facial phenotype, and developmental delay as a possible new MR/MCA syndrome. Here we report on a 2-year-old boy with similar manifestations: axial hypotonia in the first few months, prolonged feeding problems, moderate developmental delay, no speech development, deep palmar and plantar grooves, fat pads at the anteromedial aspect of the heels, and a distinct facial phenotype (high forehead, high anterior hairline, mild midfacial hypoplasia, remarkably narrow and upward slanted palpebral fissures, broad nasal ridge and tip, broad philtrum, bowed upper lip, "pouting" lower lip, full cheeks, and flat occiput). Brain MRI and MR spectroscopy studies showed relatively small frontal lobes, some widening of the lateral and third ventricles, and increased choline levels in the frontal white matter. Cytogenetic studies in lymphocytes and skin fibroblasts and whole genome micro-array CGH failed to show abnormalities. The present patient has a phenotype almost identical to that of the earlier reported children (Pierpont et al. [1998]: Am J Med Genet 75:18-21), which thereby validates this as a separate MR/MCA syndrome, appropriately designated Pierpont syndrome. The cause of the entity remains uncertain, the most likely etiologies being X-linked recessive or autosomal dominant genes.

TBL1XR1 mutations in Pierpont syndrome are not restricted to the recurrent p.Tyr446Cys mutation

“…Several malformations are described in the literature, such as Arnold‐Chiari, microcornea, retinal coloboma, hernia, anal anomalies or cryptorchidism. Two other patients with a similar phenotype were subsequently reported, including a 6‐month‐old boy with a choroid plexus papilloma (Oudesluijs, Hordijk, Boon, Sijens, & Hennekam, ; Vadivelu, Edelman, Schneider, & Mittler, ). Burkitt‐Wrigth et al reported several patients resembling Pierpont syndrome, but clinical reevaluation and molecular analyses showed that they had either Coffin‐Siris or Wiedemann‐Steiner syndrome (Burkitt‐Wright et al, ).…”

Choroid plexus papilloma and Pierpont syndrome

“…5 Only 3 cases in two cited reports have identified this as Pierpont syndrome. 4,5 No associated oncological pathology was discerned. Because gross-total resection of the brain tumor did not reverse the clinical signs of Pierpont syndrome, it is difficult to identify a direct causal relationship.…”

“…reports, no cytogenetic aberrations were detected in lymphocytes or skin fibroblasts, and analyses ruled out chromosomal mosaicism and mucopolysaccharidoses. 4,5 It remains unclear whether the inheritance pattern resembles an autosomal dominant or x-linked recessive pattern.…”

Fetal pads as a clue to the diagnosis of Pitt–Hopkins syndrome

“…TABLE I. Conditions known to be associated with prominent fetal pads [Niikawa et al, 1982;Thompson et al, 1987;Teebi et al, 1989;Hennekam et al, 1990;Romano et al, 1994;Lo et al, 1998;Lukusa and Fryns, 1998;Wilson, 1998;Bertola et al, 1999;de Vries et al, 2000;Forrester et al, 2001;Lukusa et al, 2001;Galan-Gomez et al, 2004;Grossfeld et al, 2004;Oudesluijs et al, 2005;Prescott et al, 2005;Salpietro et al, 2005;Tyson et al, 2005;Lalani et al, 2009;Reddy et al, 2009;Shimojima et al, 2009]. …”