Genetic Disorders and the Fetus. Группа авторов

hearing impairment/deafness in some members and sudden death in others may translate to the autosomal recessive Jervell and Lange–Nielsen syndrome.⁵⁹⁶ This disorder is characterized by severe congenital deafness, a long QT interval, and large T waves, together with a tendency for syncope and sudden death due to ventricular fibrillation. Given that a number of genetic cardiac conduction defects have been recognized, a history of an unexplained sudden death in a family should lead to a routine electrocardiogram at the first preconception visit and possibly mutation analysis of at least 15 long QT syndrome genes.⁵⁹⁷ Other disorders in which sudden death due to a conduction defect might have occurred, with or without a family history of cataract or muscle weakness, should raise the suspicion of myotonic muscular dystrophy (see Chapter 31).

      Rare named disorders in a pedigree should automatically raise the question of the need for genetic counseling. We have seen instances (e.g. pancreatitis) in which, in view of its frequency, the disorder was simply ascribed to alcohol or idiopathic categories. Hereditary pancreatitis, although rare, is an autosomal dominant disorder for which several genes are known.⁵⁹⁸

Awareness of the clinical manifestations in carrier females of X‐linked disorders is important given health and risk implications (Table 1.7). The pattern of inheritance of an unnamed disorder may signal a specific monogenic form of disease. For example, unexplained intellectual disability on either side of the female partner's family calls for fragile X DNA carrier testing. Moreover, unexpected segregation of a maternal premutation may have unpredicted consequences, including reversion of the triplet repeat number to the normal range.⁶⁷¹ Genetic counseling may be valuable, more especially because the phenomena of pleiotropism (several different effects from a single gene) and heterogeneity (a specific effect from several genes) may confound interpretation in any of these families.

Table 1.7 Signs in females who are carriers of selected X‐linked recessive disease pertinent to prenatal diagnosis.

Selected disorders	Key feature(s) that may occur	Selected references
Aarskog–Scott syndrome allelic with XLMR 16	Widow's peak or short stature	599
Achromatopsia	Decreased visual acuity and myopia	600
Adrenoleukodystrophy	Neurologic and adrenal dysfunction	601 , 602
Alport syndrome	Microscopic hematuria and hearing impairment	603
Ameliogenesis imperfecta, hypomaturation type	Mottled enamel vertically arranged	604
Arthrogryposis multiplex congenita	Club foot, contractures, hyperkyphosis	605
ATRX syndrome α‐thalessemia/ID syndrome	Mild intellectual disability, hemoglobin H inclusions	599 , 606
Borjeson–Forssman–Lehmann syndrome	Tapered fingers, short, widely spaced, flexed toes, mild mental retardation	607
Choroideremia a	Chorioretinal dystrophy	608
Chondrodysplasia punctata 1	Mild intellectual disability, possible bone defects and short stature	599
Chronic granulomatous disease	Cutaneous and mucocutaneous lesions	609 – 611
Cleft palate	Bifid uvula	612
Conductive deafness with stapes fixation	Mild hearing loss	613
Deafness X‐linked 1 allelic with Charcot‐Marie‐Tooth 5	Mild high‐pitch hearing loss	599
Dilated cardiomyopathy	Cardiac failure	614
Duchenne/Becker muscular dystrophy	Pseudohypertrophy, muscle weakness, cardiomyopathy/conduction defects	615 – 618
Dyskeratosis congenita	Retinal pigmentation	619
Ectodermal dysplasia	Variable severity of skin, hair, nails, and teeth	599
Emery–Dreifuss muscular dystrophy	Cardiomyopathy/conduction defects	620 – 622
Fabry disease	Angiokeratomas, corneal dystrophy, "burning" hands and feet, rhabdomyolysis	623 , 624
FG syndrome	Anterior displaced anus, facial dysmorphism	625
Fragile X syndrome	Mild‐to‐moderate intellectual disability, behavioral aberrations, schizoaffective disorder, premature ovarian failure, fragile X tremor ataxia syndrome, women and men premutation carriers	626–628 (see Chapter 16)
G6PD deficiency	Hemolytic crises, neonatal hyperbilirubinemia	629
Hemophilia A and B	Bleeding tendency	630
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