Objective

To explore the clinical and genetic characteristics of CNTNAP1 gene-related Lethal Congenital Contracture Syndrome Type 7 (LCCS7) and Congenital Hypomyelinating Neuropathy Type 3 (CHN3).

Methods

The clinical data and genetic test results of one patient were retrospectively analyzed. This patient had CNTNAP1 gene-related LCCS7 and admitted to hospital in 2013. A literature review was also conducted by searching for the CNTNAP1 gene or “Lethal Congenital Contracture Syndrome Type 7” or “Congenital Hypomyelinating Neuropathy Type 3” in databases such as CNKI, Wanfang database and PubMed. The clinical and genetic characteristics of CNTNAP1-related LCCS7 and CHN3 diseases were summarized.

Results

The proband was a female. Prenatal ultrasound showed polyhydramnios, few swallowing and respiratory movements, and a fixed fetal posture. She was born at 33 weeks due to premature rupture of membranes. After birth, she exhibited no cry, respiratory distress, and low muscle tone. She received a series of treatments in the obstetrics department, and was ultimately transferred to neonatology of our hospital due to “respiratory distress in a premature infant.” Since the fetus had abnormalities in utero, prenatal family exome sequencing was performed, which revealed two pathogenic mutations, c.1699G > T and c.789G > T, in the CNTNAP1 gene. c.1699G > T was inherited from the father, and c.789G > T was inherited from the mother, confirming compound heterozygosity. The infant died on the 13th day after premature birth. We retrieved 16 reports of CNTNAP1 gene-related LCCS7/CHN3 with 44 patients, and a total of 45 patients were analyzed combined with 1 case in this study. The main clinical manifestations included polyhydramnios (29 cases), fetal akinesia (12 cases), respiratory distress (35 cases), hypotonia (42 cases), hypomyelination (28 cases), and seizures (11 cases).

Conclusion

the CNTNAP1 gene test can be considered for polyhydramnios, fetal akinesia, postnatal respiratory distress, hypotonia, and neurological abnormalities.