Preimplantation genetic testing for monogenic disorders (PGT-M) offers an alternative strategy to prevent children from being born with hereditary neurological diseases or metabolic diseases dominated by nervous system phenotypes: a retrospective study

Abstract

Background: Preimplantation genetic testing for monogenic disorders (PGT-M) is now widely used as an effective strategy to prevent various monogenic or chromosomal diseases.

Material and methods: In this retrospective study, couples with a family history of hereditary neurological diseases or metabolic diseases dominated by nervous system phenotypes and/or carrying the pathogenic genes underwent PGT-M to prevent children from inheriting disease-causing gene mutations from their parents and developing known genetic diseases. After PGT-M, unaffected (i.e., normal) embryos after genetic detection were transferred into the uterus of their corresponding mothers.

Results: A total of 43 carrier couples with the following hereditary neurological diseases or metabolic diseases dominated by nervous system phenotypes underwent PGT-M: Duchenne muscular dystrophy (13 families); methylmalonic acidemia (7 families); spinal muscular atrophy (5 families); infantile neuroaxonal dystrophy and intellectual developmental disorder (3 families each); Cockayne syndrome (2 families); Menkes disease, spinocerebellar ataxia, glycine encephalopathy with epilepsy, Charcot-Marie-Tooth disease, mucopolysaccharidosis, Aicardi-Goutieres syndrome, adrenoleukodystrophy, phenylketonuria, amyotrophic lateral sclerosis, and Dravet syndrome (1 family each). After 53 PGT-M cycles, the final transferable embryo rate was 12.45%, the clinical pregnancy rate was 74.19%, and the live birth rate was 89.47%; a total of 18 unaffected (i.e., healthy) children were born to these families.

Conclusions: This study highlights the importance of PGT-M in preventing children born with hereditary neurological diseases or metabolic diseases dominated by nervous system phenotypes.

Keywords: Children; Hereditary neurological diseases (HND); Preimplantation genetic testing for monogenic disorders (PGT-M); Prevent.

Fig. 1

Simple flowchart for PGT-M testing

Fig. 2

Recommendations for patient management associated with hereditary neurological diseases or metabolic diseases dominated by nervous system phenotypes. Notes: Flow chart of the management of families with a childbearing history of hereditary neurological diseases or metabolic diseases dominated by nervous system phenotypes. Pediatricians and neurologists or psychiatrists are responsible for the diagnosis of hereditary neurological diseases or metabolic diseases dominated by nervous system phenotypes. Genetics specialists are responsible for genetic counseling and determining indications. Reproductive physicians are responsible for the development and implementation of the PGT-M program