Keutel syndrome: report of two novel MGP mutations and discussion of clinical overlap with arylsulfatase E deficiency and relapsing polychondritis.
Keutel syndrome is a rare, autosomal recessive disorder characterized by diffuse cartilage calcification, peripheral pulmonary artery stenosis, midface retrusion, and short distal phalanges. To date, 28 patients from 18 families have been reported, and five mutations in the matrix Gla protein gene (MGP) have been identified. The matrix Gla protein (MGP) is a vitamin K-dependent extracellular protein that functions as a calcification inhibitor through incompletely understood mechanisms. We present the clinical manifestations of three affected siblings from a consanguineous Turkish family, in whom we detected the sixth MGP mutation (c.79G>T, which predicts p.E27X) and a fourth unrelated patient in whom we detected the seventh MGP mutation, a partial deletion of exon 4. Both mutations predict complete loss of MGP function. One of the patients presented initially with a working diagnosis of relapsing polychondritis. Clinical features suggestive of Keutel syndrome were also observed in one additional unrelated patient who was later found to have a deletion of arylsulfatase E, consistent with a diagnosis of X-linked recessive chondrodysplasia punctata. Through a discussion of these cases, we highlight the clinical overlap of Keutel syndrome, X-linked chondrodysplasia punctata, and the inflammatory disease relapsing polychondritis.
Department of Pediatrics, Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
K Nicole
KN
Weaver
Moussa
M
El Hallek
Robert J
RJ
Hopkin
Kristen L
KL
Sund
Michael
M
Henrickson
Daniela
D
Del Gaudio
Adnan
A
Yuksel
Gül Ozbilen
GO
Acar
Michael B
MB
Bober
Jinoh
J
Kim
Simeon A
SA
Boyadjiev
D000015:Abnormalities, Multiple / Q000235:genetics*; D000328:Adult; D001192:Arylsulfatases / Q000235:genetics*; D002114:Calcinosis / Q000235:genetics*; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002357:Cartilage Diseases / Q000235:genetics*; D002806:Chondrodysplasia Punctata / Q000235:genetics*; D005091:Exons; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006228:Hand Deformities, Congenital / Q000235:genetics*; D006801:Humans; D008297:Male; D011081:Polychondritis, Relapsing / Q000235:genetics*; D011666:Pulmonary Valve Stenosis / Q000235:genetics*; D017384:Sequence Deletion; D055815:Young Adult; D000097568:Matrix Gla Protein
D001192:Arylsulfatases; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D000097568:Matrix Gla Protein; C110155:ARSL protein, human
ARSE; Keutel; MGP; chondrodysplasia punctata; relapsing polychondritis