Lethal cutis laxa with contractural arachnodactyly, overgrowth and soft tissue bleeding due to a novel homozygous fibulin-4 gene mutation.
Cutis laxa is characterised by redundant, inelastic skin with deep wrinkling and additional variable systemic involvement. Mutations in fibulin-4 (EFEMP2) and fibulin-5 (FBLN5) were described to be causative for autosomal recessive cutis laxa type 1 in a few families each. The female patient was born to healthy consanguineous parents. Pregnancy was remarkable for fetal overgrowth and oligohydramnios. The newborn girl showed extreme bradycardia and died perinatally. Apart from overgrowth, cutis laxa, arachnodactyly of hands and feet with contractures of the third to fifth finger, medial rotation of feet, spina bifida of the os sacrum, microcephaly and facial dysmorphism were noted. Autopsy showed collapsed lungs with hypoplastic diaphragm and signs of cervical soft tissue bleedings due to fragility of vessels. Histologic examination showed fragmentation of elastic fibres with formation of cystic cavities in the medial layer of the aorta and central lung vessels. Sequencing of the elastin, fibulin-4 and fibulin-5 genes revealed a homozygous missense mutation (p.Cys267Tyr) in the fibulin-4 gene in the patient. Our observation increases the number of cases with fibulin-4 mutations to three and extends the phenotypic spectrum of fibulin-4 mutations by microcephaly, overgrowth and arachnodactyly.
Hoyer
J
J
Institute of Human Genetics, Friedrich-Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany. jhoyer@humgenet.uni-erlangen.de
Kraus
C
C
Hammersen
G
G
Geppert
J-P
JP
Rauch
A
A
D054119:Arachnodactyly / Q000150:complications* / Q000235:genetics; D001344:Autopsy; D001483:Base Sequence; D003286:Contracture / Q000150:complications* / Q000235:genetics; D003483:Cutis Laxa / Q000150:complications* / Q000235:genetics; D004252:DNA Mutational Analysis; D004586:Electrophoresis; D005091:Exons / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D006470:Hemorrhage / Q000150:complications* / Q000235:genetics; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D011247:Pregnancy
C403672:EFEMP2 protein, human; D016326:Extracellular Matrix Proteins