Abstract
Radial ray defects comprise a large group of upper limb anomalies, ranging from partial (radial hypoplasia) to a complete (radial aplasia) deficiency of the radius with or without accompanying deficiency of the thumb and other concomitant anomalies of the upper limbs. Ultrasound evaluation of a fetus with a radial ray defect can be a diagnostic dilemma because the defect may be isolated but can also result from chromosomal aneuploidy, teratogenic exposure, and more than 200 distinct genetic syndromes, including skeletal dysplasias, particularly those associated with mesomelia. If the radius is abnormal, the thumb may also be short, hypoplastic, or absent, and evaluation of the hand for number and shape of the fingers is diagnostically important.
Keywords
radial ray defect, aneuploidy, genetic syndrome
Introduction
Ultrasound (US) evaluation of a fetus with a radial ray defect is a difficult diagnostic dilemma because the defect may be isolated, but can also result from chromosomal aneuploidy, teratogenic exposure, and more than 200 distinct genetic syndromes, including skeletal dysplasias, particularly those associated with mesomelia. Radial aplasia or hypoplasia is a rare abnormality occurring in 2 : 10,000 liveborns, but more common than isolated ulnar abnormalities. Frequently, when the radius is abnormal, the ulna is as well, as are the digits of the hands. Unilateral radial abnormalities are less likely to have an underlying genetic etiology compared to bilaterally affected limbs. Among the genetic etiologies, one of the more common disorders with radial ray anomalies is Cornelia de Lange syndrome (CDLS) ( Chapter 128 ).
Disorder
Definition
Radial ray defects comprise a large spectrum of upper limb anomalies that can range from partial (radial hypoplasia) to complete (radial aplasia) deficiency of the radius with or without accompanying deficiency of the thumb and other concomitant anomalies of the upper limbs. Some authors have classified them into four types based on their radiologic severity, with type I as the mildest and type IV showing complete absence of the radius, and there are other classification schemes which do not necessarily help identify the underlying genetic disorder.
Prevalence and Epidemiology
Isolated radial ray defects affect 2 : 10,000 newborns, though the incidence of more complicated upper limb deficiencies is approximately 5.25 : 10,000. However, if the defect is part of a genetic syndrome whether associated with aneuploidy or genetic disorders, then the prevalence is based on the incidence of the individual disorder. It is important to note that two-thirds of infants with congenital limb deficiencies have other congenital abnormalities and increased perinatal mortality and morbidity.
Etiology, Pathophysiology, and Embryology
The radius develops similarly to other appendicular bones through the process of endochondral ossification and develops from lateral plate mesoderm. Development of the limbs is under exquisite genetic control, and the genes that regulate the process are highly conserved through evolution. Radial ray deficiency is also seen in aneuploidies, including trisomy 18, 13, mosaic trisomy 16, and chromosomal microdeletion syndromes. Teratogens, specifically valproic acid, thalidomide, and aminopterin are established to cause disruption to the development of the upper limbs. Table 53.1 lists many of the disorders associated with radial ray deficiency, frequently associated with other congenital or morphologic abnormalities. Both bilaterally affected upper limbs and/or lower limbs are more likely to be associated with an underlying genetic mechanism.
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Detailed history for similarly affected children will provide diagnostic clues to recessively inherited disorders such as Fanconi anemia. Parents should be evaluated for subtle hand abnormalities, particularly their thumbs, because autosomal dominantly inherited Holt-Oram syndrome can show variable expressivity, with some affected individuals only manifesting slight thumb abnormalities and no cardiac abnormalities. Thrombocytopenia–absent radius (TAR) syndrome has a complex inheritance pattern, but is inherited as a recessive disorder. For CDLS, almost 60% of cases result from heterozygosity for mutations in the NIPBL gene that encodes for homolog of delangin. A smaller percentage of CDLS also results from heterozygosity for mutations in SMC1A, SMC3 , and RAD21 , all encoding components of the cohesin complex. There are two X-linked forms of the disease due to mutations in SMC1A and HDAC8 .
Manifestations of Disease
Clinical Presentation
Frequently, when the radius is abnormal so is the ulna. Beyond the radii and ulnae, frequently the entirety of the upper limb can be affected, including the humeri, scaphoids, trapeziums, metacarpals, and thumbs, thus the term radial ray defects is frequently used for an entire spectrum of abnormalities. Further preaxial and postaxial polydactyly, as well as oligodactyly, has been observed. Definitive diagnosis or etiology is predicated on other findings that include presence of amniotic bands, small for gestational age, facial dysmorphisms, intracranial, cardiac, gastrointestinal, genitourinary, or evidence of other skeletal abnormalities. One of the most common genetic disorders that present with radial ray defect is CDLS. This disorder presents with characteristic facial dysmorphism (maxillary prognathism, relative micrognathia, long philtrum, thin lips), low-set ears in association with prenatal and postnatal growth retardation, mental retardation and, in many cases, upper limb anomalies ( Chapter 128 ).
Technique and Findings
Ultrasound
US evaluation of all fetuses should include bilateral evaluation of all four limbs. Evidence of any discrepancy in the size of the radii or ulnae should prompt a more detailed evaluation of the fetus. The radii may appear only shortened, but straight; bowed and displaced; abnormally shaped; severe hypoplastic; and absent. If the radius is abnormal, the thumb may also be short, hypoplastic or absent, and evaluation of the hand for the number and shape of the fingers is important. A systematic approach to evaluation of the fetus should help determine if there are any other concomitant abnormalities that would provide diagnostic clues. Evaluation of the fetal facies for subtle defects in ears and mandible help refine the disorder. Cardiac defects are common in radial ray deficiency syndromes such as Holt-Oram, Nager, and Rodriquez syndromes.
CDLS has characteristic US abnormalities that include micrognathia with an overhanging top lip and low set ears ( Fig. 53.1 ), subjectively long philtrum with thin lips ( Fig. 53.2 ), and varying degrees of shortened radii and oligodactyly that frequently effects upper limbs greater than lower limbs and varies from limb to limb ( Fig. 53.3 ).
