Ege University Faculty of Medicine, Division of Pediatric Genetics, İzmir, Turkey**
Ege University Faculty of Medicine, Division of Pediatric Endocrinology, İzmir, Turkey***
Ege University Faculty of Medicine, Department of Medical Genetics, İzmir, Turkey****
Advanced Genomics and Bioinformatics Research Center (IGBAM), BILGEM, The Scientific and Technological Research Council of Turkey (TUBITAK), Kocaeli, Turkey
Lin-Gettig syndrome, described by Lin and Gettig in 1990, is a very rare autosomal recessive disease. The syndrome is characterized by craniosynostosis, severe mental retardation, absence of corpus callosum, dysmorphic facial features, camptodactyly, and hypogonadism. The molecular etiology of the syndrome has not yet been identified. In this report, we present a patient diagnosed as having Lin-Gettig syndrome via clinical findings. Molecular genetic studies have revealed that HOXC4 may be the responsible gene for this syndrome.
Due to motor-mental retardation and abnormal facial features, a 15-month-old boy was referred to our department for genetic counselling and differential diagnosis. On physical examination, his weight, height, and head circumference were measured to be 9.4 kg (10th-25th centile), 74 cm (3th-10th centile), and 43 cm (<3th centile), respectively. He had microcephaly and trigonocephaly, proptosis, downslanting palpebral fissures, midface hypoplasia, depressed nasal bridge, short columella, micrognathia, and low-set dysplastic ears. His genital examination showed micropenis, bifid scrotum, and cryptorchidism. Craniosynostosis was diagnosed using 3D computed tomography. Brain magnetic resonance imaging revealed a Chiari I malformation.
Exome sequencing of the proband showed a homozygous c. 410C>G (p.P137R) mutation in HOXC4 gene. The parents carried this mutation heterozygously. It has been considered that mutations in HOXC4 gene are the most probable candidate responsible for the underlying molecular etiology in the syndrome.
This is the first study in the literature defining a gene considered to be responsible for Lin-Gettig syndrome.