A novel disorder of sex development, characterized by progressive regression of testicular function and cystic leukoencephalopathy.
We report a novel syndromic disorder of sex development observed in three male siblings, presenting with the association of micropenis without hypospadias, cryptorchidism, very low level of antimüllerian hormone in the neonatal period, and no persistent müllerian duct structures, suggesting a progressive regression of testicular function. The patients described here showed a striking neurological involvement including bilateral periventricular cysts observed in the anterior part of the frontal horns prenatally and increasing in size and number over time, associated with infra and supratentorial parenchymal atrophy, dilated ventricular system, corpus callosum hypoplasia, severe intellectual disability, and epilepsy. Associated features included a distinctive facies, joint contractures, retinopathy, and hearing loss. Pathological examination was consistent with testicular dysgenesis and leukoencephalopathy with spongiosis and microcalcifications. To the best of our knowledge, this disease, characterized by a recognizable pattern of malformations, has not been previously reported. An exhaustive genetic and metabolic evaluation was normal. Autosomal recessive inheritance was considered to be likely, on the basis of SNP studies. We hope that the detailed description provided here of the clinical, radiological, and pathological findings observed in this family will help to identify further unrelated patients, and ultimately, to clarify the genetic basis of this condition. © 2017 Wiley Periodicals, Inc.
Service de Génétique, Centre de Référence Anomalies du Développement, Hospices Civils de Lyon, Bron, France.|INSERM U1028, CNRS UMR5292, Centre de Recherche en Neurosciences de Lyon, GENDEV Team, Université Claude Bernard Lyon 1, Bron, France.
Massimiliano
M
Rossi
Service d'Anatomie Pathologique, Hospices Civils de Lyon, Bron, France.
Alexandre
A
Vasiljevic
Service de Génétique, Centre de Référence Anomalies du Développement, Hospices Civils de Lyon, Bron, France.
Audrey
A
Labalme
Service d'Anatomie Pathologique, Hospices Civils de Lyon, Bron, France.
Frédérique
F
Dijoud
Service d'Endocrinologie Moléculaire et Maladies Rares, Hospices Civils de Lyon, Bron, France.
Delphine
D
Mallet-Motak
Service d'Anatomie et Cytologie Pathologiques, CHU de Saint-Etienne, Saint-Priest-en-Jarez, France.
Carmen Adina
CA
Petcu
Service de Génétique Clinique, Chromosomique et Moléculaire, Centre de Référence des Anomalies du Développement, CHU de Saint-Etienne, Saint-Priest-en-Jarez, France.
Renaud
R
Touraine
Service des Maladies Héréditaires du Métabolisme et Dépistage Néonatal, Hospices Civils de Lyon, Bron, France.
Christine
C
Vianey-Saban
Service d'Imagerie Pédiatrique et Fœtale, Hospices Civils de Lyon, Bron, France.
Laurent
L
Guibaud
Service de Génétique, Centre de Référence Anomalies du Développement, Hospices Civils de Lyon, Bron, France.|INSERM U1028, CNRS UMR5292, Centre de Recherche en Neurosciences de Lyon, GENDEV Team, Université Claude Bernard Lyon 1, Bron, France.
Patrick
P
Edery
Service de Génétique, Centre de Référence Anomalies du Développement, Hospices Civils de Lyon, Bron, France.|INSERM U1028, CNRS UMR5292, Centre de Recherche en Neurosciences de Lyon, GENDEV Team, Université Claude Bernard Lyon 1, Bron, France.
Damien
D
Sanlaville
Service d'Endocrinologie Moléculaire et Maladies Rares, Hospices Civils de Lyon, Bron, France.
Yves
Y
Morel
D001921:Brain / Q000473:pathology; D002675:Child, Preschool; D012734:Disorders of Sex Development / Q000175:diagnosis* / Q000235:genetics*; D019066:Facies; D017809:Fatal Outcome; D005832:Genital Diseases, Male / Q000473:pathology; D006059:Gonadal Dysgenesis / Q000175:diagnosis* / Q000235:genetics*; D012739:Gonadal Steroid Hormones / Q000097:blood; D006801:Humans; D007231:Infant, Newborn; D056784:Leukoencephalopathies / Q000175:diagnosis* / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D010413:Penis / Q000002:abnormalities / Q000473:pathology; D010641:Phenotype; D035781:Siblings; D013577:Syndrome; D013737:Testis / Q000002:abnormalities*
D012739:Gonadal Steroid Hormones
brain cysts; gonadal dysgenesis; intellectual disability; leukoencephalopathy