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 |
|
Hypohydrotic ectodermal dysplasia
|