Abstract
Background: Néstor-Guillermo progeria syndrome (NGPS; OMIM 614008) is caused by biallelic pathogenic variants in BANF1 (barrier-to-autointegration factor 1) on chromosome 11q13. It characterized by early onset and slow progression of symptoms including poor growth, lipoatrophy, pseudo-senile facial appearance, and normal cognitive development. Two adult patients have been reported. This is the first reported case of a child with NGPS who presented to endocrine clinic with failure to grow.
Clinical Case: Two year, 8 month old Hispanic female born at 40 weeks gestation with birth weight 3.5 kg. At 1 year, she had short stature, poor weight gain, and thinning hair. There were no developmental concerns. Family history was remarkable for consanguinity. At presentation, her weight was 8.5 kilograms) and height 80 centimeters (both <1st percentile) and head circumference 45.5 centimeters (3rd percentile). Hair was sparse and fine with large areas of scalp alopecia. She had a small face with overhanging brow ridge, flattened midface, narrow nose, small mouth and bilateral lower eyelid ectropion. Fingers were shortened with thickened knuckles, widened fingertips, and distally set nails. Skin was tight throughout, particularly notable on the legs and hands with light discoloration of skin over the hand joints and reticulated dark macules over the lower abdomen. Her cardiac, respiratory, abdominal, genitourinary, neuro and joint examinations were unremarkable. Routine labwork was normal. Her bone age was normal at 2 year and 7 months but there was hypoplasia of the distal phalanges. Full skeletal survey revealed small mandible, thinning of the cranial vault, apparent crowding of the teeth, short stature, acroosteolysis-like changes involving the distal phalanges most evident in the hands, pointed distal phalanx of the great toes, and resorption of the distal clavicles. Her echocardiogram was normal. Sequencing and deletion/duplication analysis of LMNA was not diagnostic. Trio-based whole exome sequencing (WES) was performed after obtaining informed consent. WES revealed homozygosity for a pathogenic missense variant in BANF1 c.34G>A (p.Ala12Thr) inherited from each of the unaffected parents.
Conclusion: Progeria syndromes are unusual but diagnosable causes of failure to grow and can be diagnosed based on clinical suspicion. This patient represents the first child reported with NGPS.
Idiopathic short stature due to novel heterozygous mutation of the aggrecan gene
