Читать книгу Genetic Disorders and the Fetus - Группа авторов - Страница 56

 Ablepharon–macrostomia syndrome

 Adult‐onset idiopathic dystonia

 Autosomal dominant acute myelogenous leukemia

 Autosomal dominant familial spastic paraplegia

 Autosomal dominant polycystic kidney disease (PKD1)

 Autosomal dominant rolandic epilepsy

 Behçet syndrome

 Bipolar affective disorder

 Crohn disease

 Facioscapulohumeral muscular dystrophy

 Familial adenomatous polyposis

 Familial breast cancer

 Familial chronic myeloproliferative disorders

 Familial Hodgkin lymphoma

 Familial intracranial aneurysms

 Familial pancreatic cancer

 Familial paraganglioma

 Familial Parkinson disease

 Familial primary pulmonary hypertension

 Familial rheumatoid arthritis

 Graves disease

 Hodgkin and non‐Hodgkin lymphoma

 Holt–Oram syndrome

 Idiopathic pulmonary fibrosis

 Lattice corneal dystrophy type I (LCD1)

 Li–Fraumeni syndrome

 Ménière disease

 Obsessive–compulsive spectrum disorders

 Oculodentodigital syndrome

 Paroxysmal kinesigenic dyskinesia (PKD)

 Restless legs syndrome

 Schizophrenia

 Total anomalous pulmonary venous return

 Unipolar affective disorder

Recognition in the last decade of hexanucleotide repeat expansions in the C9orf72 gene reveal additional challenges that have raised consideration of prenatal diagnosis, as discussed under “Accurate diagnosis.” Mutations in C9orf72 have been reported in 40–50 percent of cases with familial amyotrophic lateral sclerosis, between 3.5 percent and 8 percent of sporadic ALS cases,^792–795 and in 25 percent of familial frontotemporal lobar degeneration, with about 7 percent in sporadic cases.^{793, 794} The clinical spectrum includes patients with frontotemporal dementia and ALS as well as those with a corticobasal syndrome.⁷⁹⁶ The real burden and likely involvement of prenatal diagnosis is the recognition of C9orf72 expansions noted in Western Europe as occurring in 18.52 percent of familial cases and 6.26 percent in sporadic cases of frontotemporal lobar degeneration.⁷⁹⁷ Overall frequencies of these expansions in Finland, Sweden, and Spain were much higher, being 29.33 percent, 20.73 percent, and 25.49 percent, respectively.⁷⁹⁷ A further distressing aspect of the C9orf72 expansion is the symptomatology that extends to family members who do not have the expansion. In a study of 1,414 first‐ and second‐degree relatives, a statistically significant number had an increased risk of schizophrenia (hazard ratio of 4.9), late‐onset psychosis, and suicide.⁷⁹⁸ There is also evidence of anticipation.⁷⁹⁹

Preimplantation genetic testing (see Chapter 2) has been successful for many repeat expansion disorders including fragile X syndrome (see Chapter 16), Huntington disease, myotonic muscular dystrophy, and spinocerebellar ataxias types 2 and 12.^800–802