Introduction: Acromesomelic Dysplasia of Maroteaux (AMDM) is a cause of severe short stature (final height below120cm) with shortening of the middle and distal segments of the limbs, caused by homozygous or heterozygous mutations in the NPR2 gene which encodes natriuretic peptide receptor B on chromosome 9p13
Case report: The proband was 4y6mo old, second born to 3rd degree consanguineous parents and presented with concerns of short stature. His height was 81 cm(z-score -5.1) and weight was 13kg(z-score -1.6). His intelligence was noted to be normal. Phenotypically, he had frontal bossing, arched eyebrows, long eyelashes, fanning ears, short nose and small teeth. Characteristically, he had mesomelic and acromelic shortening with brachydactyly in both upper and lower limbs. There was laxity of joints. The spine seemed grossly normal.
Skeletal survey also revealed acromesomelic shortening and delayed bone age. Investigations revealed a low IGF-1- 18.9 ng/ml (Normal-50-286ng/ml) and had failed two separate growth hormone stimulation tests. The rest of the hormonal profile was normal.
Focused exome sequence analysis revealed an apparently homozygous indel variation in exon -1 of the Natriuretic peptide receptor 2 (NRP2) gene on Chromosome 9 (c.663-664delGCinsAA p.Arg222Ser). This variant has not been previously reported in individuals with this disease and has also not been observed in the general population. It was found to be potentially deleterious by PolyPhen-2 and SIFT bioinformatics tools.
Clinically the proband was suspected to have an Acromesomelic dysplasia-Maroteaux type and it was substantiated genetically by the above finding.
Due to concomitant Growth hormone deficiency, he was started on recombinant Growth firstname.lastname@example.org/kg/day.
On 6 month follow up, he had shown a favourable height gain of +4cm on Growth hormone.
Conclusion: The C-type natriuretic peptide and its receptor NPR-B are recognized as important regulators of longitudinal growth. Variations in the encoding genes (NPR2 gene) must be considered in short stature presenting with acromesomelic skeletal dysplasia. Genetic counselling plays an important part of management in the above disorder
19 - 21 Sep 2019
European Society for Paediatric Endocrinology