Seminars in Fetal & Neonatal Medicine (2005) 10, 221e231 www.elsevierhealth.com/journals/siny Common neonatal syndromes Mark H. Lipson* Department of Genetics, Permanente Medical Group, Sacramento, CA, USA KEYWORDS Summary The process of diagnosis of genetic syndromes in the newborn period is Fluorescence in situ carried out in the context of parental anxiety and the grief following an often- hybridisation (FISH); unexpected outcome after a long pregnancy. The nursery staffs invariably have Telomere; a strong interest in giving the family proper information about prognosis. This Uniparental disomy; article is intended to focus on an approach to the diagnosis of genetic syndromes Imprinting and to discuss specific syndromes that may be seen with some frequency in the nursery. Ó 2005 Elsevier Ltd. All rights reserved. A baby has just been born. The exhausted but a geneticist or genetics centre is essential at some jubilant parents are finally able to see the result of point in the diagnostic process. A diagnosis is not the previous 9 months of morning sickness, weight the end of the process but merely the beginning. gain and water retention. But instead of unmiti- Genetic counseling is a process whereby a con- gated excitement and happiness, there is fear, firmed or possible genetic condition is reviewed uncertainty and disbelief. The reaction of the with the family, and the etiology, natural history, nurses and doctors has indicated that there is prognosis, treatment possibilities, risk of recur- a problem with the baby. What does it mean? Will rence, potential for prenatal diagnosis and the the baby be OK? What can be done to correct the availability of pertinent reading materials and problem? It is in this context that syndrome support groups are discussed at length. The emo- identification takes place. It is a very difficult time tional and psychological aspects of the situation for both the family and the medical staff. A rapid are also explored.1 This process usually takes diagnosis and treatment plan are desired, but this place over the course of several meetings with the is often not possible. family. Although the initial evaluation can be performed This review covers a general approach to making by the pediatrician or neonatologist, referral to a diagnosis in a newborn with anomalies, and describes some of the common syndromes one encounters in the nursery. Several textbooks are * Tel.: C1 916 614 4785; fax: C1 916 614 4985. recommended for obtaining more information 2e4 E-mail address: [email protected] about these syndromes. 1744-165X/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.siny.2005.02.003 222 M.H. Lipson Multiple congenital anomalies Down syndrome Taking a detailed pregnancy history is essential e In the past, this was the most common syndrome it is the starting point of all evaluations of the identified in the newborn period, despite the newborn. A pedigree is also very important. A availability of chorionic villus sampling and amnio- three-generation pedigree is usually obtained in centesis for advanced maternal age. However, with 10e15 min and can be invaluable. Clues from the the advent of prenatal screening programs aimed at type and pattern of anomalies or abnormal preg- detecting Down syndrome in the second and more nancies in family members can point to a certain recently the first trimester, the incidence at birth of type of inheritance pattern or chromosome prob- Down syndrome has decreased. Due to false-nega- lem. It is easier to identify this type of information tive testing and a significant number of women from a pedigree than from a series of family choosing either not to have screening or not to have history questions. amniocentesis after a positive screen, or choosing The physical examination focuses on describing to continue a pregnancy after amniocentesis makes the birth defects and minor anomalies/dysmorphic a definitive diagnosis, Down syndrome continues to features. Determining which features are impor- still be a condition commonly presenting in the tant in syndrome identification is challenging. newborn period. Examining other family members or looking at The condition is usually not hard to identify family photos can be very helpful in determining (Fig. 1). However, if the newborn is premature, whether a dysmorphic feature is a normal family particularly less than 34 weeks’ gestation, Down variant or a unique finding that may be part of syndrome may be difficult or nearly impossible to a syndrome. suspect. The typical facial features of up-slanting Deciding on laboratory testing comes next. If palpebral fissures, flat facies and small ears (less there are birth defects or significant unexplained than 3 cm in vertical length) are well known to dysmorphic features, a chromosome study needs clinicians. In addition, the gestalt of the facial to be undertaken. A satisfactory study is one that expression when the child cries is particularly has a minimum of about 550 bands. If a routine a useful finding. The hands also give important chromosome study is normal, additional studies clues to the diagnosis. Fifth finger clinodactyly, may be considered necessary looking for submi- usually bilateral, is very frequent. Simian lines are croscopic abnormalities by a technique called also common but are present in a significant fluorescence in situ hybridisation (FISH).5 This percentage of the general population. Significant technique is based on the hybridisation of a piece hypotonia may be the initial finding. The best- of labeled DNA, a probe, to a complementary area known characteristic associated birth defects seen on a chromosome. Specific probes are available for each chromosome. Submicroscopic deletions or rearrangements at the ends (telomeres) of the chromosome, performed as a telomeric FISH study, are a recognised cause of malformations.6 Obtaining plain X-rays are useful in more pre- cisely evaluating anomalies of the extremities. Certain anomalies are associated with defects in other areas of the body and therefore require evaluation. Examples are heart defects with thumb anomalies (HolteOram syndrome) and renal defects and optic nerve coloboma (renalecoloboma syn- drome).7 Cranial imaging for micro/macrocephaly and hypo/hypertelorism is also recommended. Where laboratory studies are normal and the diagnosis is unclear, a review of the literature and syndrome textbooks can be useful. Online Mendelian Inheritance in Man (OMIM), an on-line continuously updated catalog of human genes and genetic disorders, is an extremely useful human genetic resource. It is available free of charge. Additionally, there are software dysmorphology Figure 1 Up-slant to palpebral fissures and low nasal databases that can be purchased. bridge in Down syndrome. Common neonatal syndromes 223 in Down syndrome are duodenal atresia and atrio- tissue to tissue. That is to say, although 30% of the ventricular canal defects. Some form of congenital cells in the blood may be normal and 70% may be heart defect is by far the most common associated trisomy 21, it cannot be predicted what the birth defect, with about 40% of patients being percentage mix will be in the heart, kidney or, affected. Less well-known defects include Hirsch- most importantly, the brain. Given this uncertainty, sprung disease and congenital hypothyroidism. A it is best to not predict a much better prognosis prenatal finding of mild dilatation of the cerebral based on mosaicism. Life expectancy, given access ventricular atria (10e11 mm) without overt hydro- to appropriate medical and surgical interventions, cephalus is not infrequent. Special growth charts is in the range of 50e60 or more years. for Down syndrome patients are available, and the American Academy of Pediatrics has published health supervision guidelines. The confirmatory diagnosis for Down syndrome is Trisomy 13 and 18 a conventional chromosome study. Even in cases where the diagnosis is obvious, it is important to do These chromosomal disorders are, like Down the study. In about 95% of the cases (more with an syndrome, associated with advanced maternal older mother), the Down syndrome baby will have age. The incidence at birth has fallen over time a standard non-dysjunction karyotype (47,C21). as second-trimester ultrasound screening in preg- Doing chromosome studies on the parents in such nancy has become more routine and affected cases are not necessary. The risk of recurrence in pregnancies terminated. Expanded alpha fetopro- non-dysjunction Down syndrome is about 1% for tein screening will detect many cases of trisomy 18 younger women and is not increased above the but does not identify trisomy 13. Continuation of age-related Down syndrome risk for women in their pregnancy after confirmation of these trisomies is mid-30s and older. much rarer than with Down syndrome. Most fetuses Down syndrome will occasionally be due to with these trisomies do not survive to delivery. a translocation. A family history may be the first Multiple birth defects are common in both the clue if there is a history of other Down syndrome conditions but are much more frequent in trisomy offspring in the extended family. The usual situa- 13 (Figs. 2 and 3). Some babies with trisomy 18 tion is a Robertsonian translocation involving have little in the way of anomalies but may be small a fusion chromosome 14 and 21 (46,t14/21), but for gestational age. The combination of growth other combinations are possible. Chromosome retardation and polyhydramnios is especially sug- studies on the parents of a translocation Down gestive of trisomy 18. syndrome baby are very important for proper Both conditions have facial dysmorphism. The genetic counseling. The risk of recurrence where classical trisomy 13 baby will have microcephaly, one of the parents carries a balanced translocation iris coloboma, abnormally shaped ears and cleft lip ranges from less than 1% to as high as 10% based on the type of translocation and the sex of the carrier parent.8 A Down syndrome baby will occasionally be born with a 21/21 translocation (46,t21/21).