Familly with two different cases of post- and pre-natal l1 syndrome: When hydrocephaly become “multidisciplinary headache”

Abstract

In middle 90?s the scientific community classified as CRASH syndrome a clinical situation characterized by Corpus callosum hypoplasia, Retardation, Adducted thumbs, Spastic paraplegia, and Hydrocephalus. This pathology is also known as L1 syndrome and includes a spectrum of related neurological disorders with an X-linked recessive mode of inheritance associated to mutations in the human L1 Cell Adhesion Molecule gene (L1CAM;OMIM 308840). Here we report regarding a couple pass through our Genetic Counseling, during clinical diagnostic procedure in ~3 years old son, due to presence of multiple malformations such as hydrocephalus, agenesis of corpus callosum, tetraparesys, axial hypotony, cognitive and motor incompetency. The proband was the first male child of a healthy, non-consanguineous Italian couple with no family history of brain abnormalities, recurrent miscarriages, other birth defects and/or genetic illnesses. During Genetic Counseling, a diagnostic hypothesis of L1 syndrome was made, with in deep explanation of genetic testing possibilities. On the basis of our protocol, we fixed another appointment 2 weeks later, but unfortunately the family never showed up. Approximately one year later, the Department of Gynecology and Obstetrics requested Genetic Counseling for a 33 years old woman, secondigravida (22? gestation week), with abnormal ultrasound findings showing severe fetal ventriculomegaly. The family history was unremarkable with no consanguinity; she was one of two sisters and had a healthy brother. Surprisingly the woman was the mother of our proband. On the basis of a diagnostic hypothesis of L1 syndrome (includes a spectrum of related neurological disorders with an X-linked recessive mode of inheritance), we performed molecular analysis on the proband?s DNA, mother?s DNA and fetal DNA. The mutational screening revealed the presence of a non sense c.2701C>T (p.Arg901