A Novel Variant in the AGPS Gene Causes the Rare Rhizomelic Chondrodysplasia Punctata Type 3: A Case Report

Abstract

Rhizomelic chondrodysplasia punctata (RCDP) is a devastating medical condition for patients and their families. It is a rare peroxisomal autosomal recessive disorder. It was recognized clinically with skeletal abnormalities and intellectual disabilities mainly due to plasmalogen deficiency. Here, we report a case of a 16-day-old girl who was referred to King Abdulaziz Medical City Jeddah, Saudi Arabia because of dysmorphic features. Her growth parameters were below the 3rd centile with short proximal long bones and multiple joint contractures in the extremities. The radiographs showed rhizomelic and shortening of both humeri and femurs. Moreover, punctate ossification was identified in the upper spine, humeri around the shoulders, and femurs around the knees. We observed other classical features, and the genetic testing confirmed the diagnosis of RCDP type 3. Although RCDP is a rare condition, it is a distressing burden necessitating early diagnosis and a holistic approach for management.

Neonatal rhizomelic chondrodysplasia punctata type 2 caused by a novel homozygous variant in the GNPAT gene

“…His skeletal survey showed discrete punctate cartilaginous calcifications and a short proximal skeleton, likely CDP. The dysmorphic facial features were also noted in the earlier report of a 16‐day‐old baby girl from Saudi Arabia, where she had low set ears, long philtrum, and upslanting palpebral fissures of both eyes 9 . Our case report had similar findings with a depressed nasal bridge, broad nose, coarse facial features, and long philtrum.…”

“…In addition, no prior history of drug or alcohol use or any symptoms was observed 10 . A bilateral polar cataract was observed in this case, comparable to an earlier reported case with congenital cataracts in three reported patients 9 . The disease was explained to the parents whose children were provided genetic counseling.…”

“…The dysmorphic facial features were also noted in the earlier report of a 16‐day‐old baby girl from Saudi Arabia, where she had low set ears, long philtrum, and upslanting palpebral fissures of both eyes. 9 Our case report had similar findings with a depressed nasal bridge, broad nose, coarse facial features, and long philtrum. The baby had multiple contractures at the thigh, knee, shoulder, elbow, wrist, and fingers (arthrogryposis multiplex congenita).…”

“…A bilateral symmetry in the shortening of the humerus and femur with punctate epiphysis due to stippled calcification was observed, and diaphyseal thickening with metaphyseal splaying and fraying was noted. There was a previously reported case of RCDP type 3 with a novel AGPS genetic variant, where punctate calcifications were seen in the proximal humerus, proximal femur, and upper spine 9 . His differential diagnosis includes genetically inherited CDPs, with maternal autoimmune disease, exposure to warfarin, and fetal alcohol syndrome.…”

“…There was a previously reported case of RCDP type 3 with a novel AGPS genetic variant, where punctate calcifications were seen in the proximal humerus, proximal femur, and upper spine. 9 His differential diagnosis includes genetically inherited CDPs, with maternal autoimmune disease, exposure to warfarin, and fetal alcohol syndrome. The mother tested negative for autoimmune disease in the lab.…”