Matthew-Wood syndrome: report of two new cases supporting autosomal recessive inheritance and exclusion of FGF10 and FGFR2.
We describe two fetal cases of microphthalmia/anophthalmia, pulmonary agenesis, and diaphragmatic defect. This rare association is known as Matthew-Wood syndrome (MWS; MIM 601186) or by the acronym "PMD" (Pulmonary agenesis, Microphthalmia, Diaphragmatic defect). Fewer than ten pre- and perinatal diagnoses of Matthew-Wood syndrome have been described to date. The cause is unknown, and the mode of transmission remains unclear. Most cases have been reported as isolated and sporadic, although recurrence among sibs has been observed once. Our two cases both occurred in consanguineous families, further supporting autosomal recessive transmission. In addition, in one family at least one of the elder sibs presented an evocatively similar phenotype. The spatiotemporal expression pattern of the FGF10 and FGFR2 genes in human embryos and the reported phenotypes of knockout mice for these genes spurred us to examine their coding sequences in our two cases of MWS. While in our patients, no causative sequence variations were identified in FGF10 or FGFR2, this cognate ligand-receptor pair and its downstream effectors remain functional candidates for MWS and similar associations of congenital ocular, diaphragmatic and pulmonary malformations.
Martinovic-Bouriel
Jelena
J
Assistance Publique - Hôpitaux de Paris, Hôpital Necker - Enfants Malades, Department of Genetics, Embryo-Fetal Pathology Unit, Paris, France. jelena.martinovic@nck.aphp.fr
Bernabé-Dupont
Céline
C
Golzio
Christelle
C
Grattagliano-Bessières
Bettina
B
Malan
Valérie
V
Bonnière
Maryse
M
Esculpavit
Chantal
C
Fallet-Bianco
Catherine
C
Mirlesse
Véronique
V
Le Bidois
Jerôme
J
Aubry
Marie-Cécile
MC
Vekemans
Michel
M
Morichon
Nicole
N
Etchevers
Heather
H
Attié-Bitach
Tania
T
Encha-Razavi
Féréchté
F
Benachi
Alexandra
A
D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000853:Anophthalmos / Q000175:diagnosis / Q000235:genetics*; D025063:Chromosome Disorders / Q000175:diagnosis / Q000473:pathology; D005260:Female; D051526:Fibroblast Growth Factor 10 / Q000235:genetics*; D005808:Genes, Recessive; D006801:Humans; D008168:Lung / Q000002:abnormalities*; D008297:Male; D008850:Microphthalmos / Q000175:diagnosis / Q000235:genetics*; D011247:Pregnancy; D011296:Prenatal Diagnosis; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D013577:Syndrome
C496463:FGF10 protein, human; D051526:Fibroblast Growth Factor 10; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2