Frontometaphyseal dysplasia 1 in a patient from Sri Lanka.

A Sri Lankan male child with supraorbital hyperostosis, broad nasal bridge, small mandible, severe kyphoscoliosis, distal joint contractures of the hands and long second and third toes is described. A hemizygous pathogenic variant in exon 22 of the filamin A (FLNA) gene [NM_001110556.1: c.3557C>T; which leads to a nonsynonymous substitution of serine by leucine at codon 1186 in the FLNA protein; NP_001104026.1: p.Ser1186Leu] was identified. The clinical features observed in this patient were consistent with the cardinal manifestations seen in frontometaphyseal dysplasia 1 (FMD1). However, characteristic extra skeletal manifestations such as cardiac defects, uropathy, and hearing impairment which have previously been reported in association with this condition were absent in this patient.

Mutations in ANTXR1 cause GAPO syndrome.

The genetic cause of GAPO syndrome, a condition characterized by growth retardation, alopecia, pseudoanodontia, and progressive visual impairment, has not previously been identified. We studied four ethnically unrelated affected individuals and identified homozygous nonsense mutations (c.262C>T [p.Arg88*] and c.505C>T [p.Arg169*]) or splicing mutations (c.1435-12A>G [p.Gly479Phefs*119]) in ANTXR1, which encodes anthrax toxin receptor 1. The nonsense mutations predictably trigger nonsense-mediated mRNA decay, resulting in the loss of ANTXR1. The transcript with the splicing mutation theoretically encodes a truncated ANTXR1 containing a neopeptide composed of 118 unique amino acids in its C terminus. GAPO syndrome's major phenotypic features, which include dental abnormalities and the accumulation of extracellular matrix, recapitulate those found in Antxr1-mutant mice and point toward an underlying defect in extracellular-matrix regulation. Thus, we propose that mutations affecting ANTXR1 function are responsible for this disease's characteristic generalized defect in extracellular-matrix homeostasis.

Persistent lingual ulceration (Riga-Fede disease) in an infant with Down syndrome and natal teeth: a case report.

INTRODUCTION: Riga-Fede disease is a rare pediatric condition in which chronic lingual ulceration results from repetitive trauma. Neonatal teeth or underlying neuro-developmental disorders which include Down syndrome are described as causative factors, but to the best of our knowledge, this is the first case report of both Down syndrome and natal teeth coexisting. The need for early extraction in the presence of two risk factors is highlighted in this case report. CASE PRESENTATION: An 18-month-old Sinhalese male presented with an ulcerating lingual mass on the ventral surface of the tongue. The lesion had progressed over the past six months. He also had clinically diagnosed Down syndrome.The ulcer was non-tender, indurated, and had elevated margins. It was not bleeding and two natal teeth in lower central dentition were seen in apposition with the lesion. There was no regional lymphadenopathy but the ulcer was causing concerns as it mimicked a malignant lesion. A clinical diagnosis of Riga-Fede disease caused by raking movements of the tongue against anterior natal teeth by a child who was developmentally delayed and prone to suck on his tongue was made. The mother was reassured and the natal teeth were extracted. CONCLUSIONS: Early extraction of natal teeth is recommended only if there is a risk of aspiration or interference with breast feeding. Although Down syndrome is among the neuro-developmental conditions that lead to this lesion, its occurrence is usually at an older age. The presence of natal teeth together with Down syndrome caused the lesion to occur in infancy. Awareness of the benign nature of this rare condition by pediatricians and dental practitioners is important as it will allay anxiety and avoid unnecessary biopsy. This case also highlights the impact of two risk factors and needs consideration as an added indication for the early extraction of natal teeth.