Hypothesis: Symbrachydactyly.

The term symbrachydactyly has been used for the phenotype of two or three short fingers or toes, hypoplasia of the middle and distal phalanges and variable syndactyly of the affected digits. Some clinicians have extended this diagnosis to include other phenotypes, specifically cleft hand, terminal transverse limb defects, hypoplasia of the thumb and fifth finger with nubbins for fingers 2, 3, and 4 and the hand deformity of the Poland anomaly. A malformations surveillance program can identify enough affected infants to characterize a phenotype. In the Active Malformations Surveillance Program in Boston (1972-2012) among 289,365 births, all infants and fetuses with structural abnormalities were identified from reading the examination findings by the pediatricians and pathologists and the results of diagnostic tests. Liveborn and stillborn infants were included, as well as fetuses from elective terminations because of anomalies identified in prenatal testing. We present the findings in 14 infants, all liveborn, who had symbrachydactyly of one or both hands (n = 12) or feet (n = 2). We suggest restricting the term symbrachydactyly to this single phenotype to improve counseling and to focus future research on identifying the cause(s).

Hypothesis: Central digit hypoplasia.

Limb deficiencies are a common birth defect. A malformations surveillance program among many newborns, stillborn fetuses, and malformed fetuses in elective terminations can identify a sufficient number of infants with the same set of abnormalities to characterize a specific limb deficiency phenotype. The active malformations surveillance program was carried out among 289,365 births at Brigham and Women's Hospital in Boston over a 41-year period (1972-2012). The research assistants identified the affected infants and fetuses from reading the findings recorded in each newborn's medical record by the examining pediatricians and consultants and by the pathologists in autopsies. One hundred ninety-four newborn infants and fetuses were found to have a limb deficiency either as an isolated abnormality or as one of multiple malformations. We identified three phenotypes of limb deficiency. We present here the seventeen infants and fetuses with "central digit hypoplasia," a term we suggest for this phenotype: hypoplasia of the thumb and fifth finger with nubbins of soft tissue in place of fingers 2, 3, and 4 at the level of the metacarpal-phalangeal joint. Central digit hypoplasia is to be distinguished primarily from the terminal transverse limb defect that ends at the wrist. In symbrachydactyly, the middle and distal phalanges of the fingers and toes are hypoplastic. In addition, central digit hypoplasia should be distinguished from the amniotic band syndrome, the most common and incorrect diagnosis suggested by the pediatricians and the consultants in this survey. The affected infant and her/his parents benefit from more accurate and specific counseling.

Terminal transverse limb defects with "nubbins".

BACKGROUND: A terminal transverse limb defect with absence of the forearm and hand or just the hand is an uncommon limb deformity in an otherwise healthy newborn. Most of the affected infants also have tiny digit-like nubbins on the stump of the affected limb, a finding that could represent an attempt at regeneration following vascular obstruction in early limb development. METHODS: One hundred ninety-four newborn infants with a limb deficiency were identified among 289,365 births in an active malformations surveillance program at Brigham and Women's Hospital in Boston, MA from 1972 to 2012. Twenty-eight infants with terminal transverse limb defects were identified. RESULTS: Twenty-four had tiny digit-like nubbins (0.5 cm in length) on the stump at one of three levels: the proximal portion of the forearm, the wrist or the forefoot. The examination of the placentas of eight affected infants showed no evidence of amnion rupture. Three of these 28 infants had associate chromosome abnormalities: trisomy 21, chromosome 11q deletion and the deletion of 22q11.2. CONCLUSION: Terminal transverse limb defects reflect failure of early limb development. Awareness of this phenotype at birth, or when identified by ultrasound screening, can provide more accurate counseling than occurs with the more common misdiagnosis of "amniotic band syndrome."

Limited surface examination to evaluate potential teratogens in a resource-limited setting.

BACKGROUND: To determine the frequency of malformations that would be identified in the limited surface examination of a newborn by the delivering nurse midwife in a resource-limited setting. METHODS: The limited surface examination will identify visible external anomalies, but not abnormalities inside the mouth, most heart defects, undescended testes, inguinal hernias, hip dysplasia, peripheral vascular anomalies, and some internal anomalies. The findings in a malformations surveillance program, involving 289,365 births in Boston, have been used to establish the prevalence rate of malformations that would be identified and not identified. In African countries, the number of anomalies to be identified should also be reduced by excluding polydactyly, postaxial, type B, a common minor finding, from the list of potential malformations. RESULTS: Of note, 2.05% (n = 5,941) of the 289,365 births surveyed had one or more malformations. The abnormalities that would have been missed, using surface exam alone, accounted for 0.5% of all of malformations identified and reduced the overall prevalence rate of malformations to 1.5%. In addition, excluding all infants with isolated postaxial polydactyly, type B reduced the expected prevalence rate of malformations to 1.3% in unexposed newborn infants. CONCLUSION: A limited surface examination can detect the majority of malformations among newborn infants.

Malformations among infants of mothers with insulin-dependent diabetes: Is there a recognizable pattern of abnormalities?

BACKGROUND: Infants of diabetic mothers have been shown in several studies to have an increased frequency of malformations. In previous studies, an increased frequency of several specific malformations has been noted, including anencephaly, bilateral renal agenesis, and double outlet right ventricle. Surveillance, used to identify all malformed infants in a consecutive sample of births, can identify a distinctive pattern of malformations among the affected infants. METHODS: The infants of insulin-dependent, pregestational diabetic mothers were identified in the daily review of the medical records of each newborn infant with a malformation and her/his mother's medical record. Infants of mothers with gestational diabetes were excluded. The frequency of each malformation was compared to that among the malformed infants of nondiabetic mothers. RESULTS: One hundred and eighty-three malformed infants of diabetic mothers were identified among the 289,365 births. The most notable malformations were: neural tube defects (anencephaly, 9%), heart defects (transposition of great arteries, 4%), bilateral renal agenesis or dysgenesis (6%), and vertebral anomalies (hemivertebrae, 4%). CONCLUSIONS: There was a recognizable pattern of malformations and characteristics of infants of diabetic mothers, although there was variation in the pattern among affected infants. Some of the malformations in the diabetic embryopathy can be identified in prenatal screening by ultrasound. More important, their occurrence can be reduced significantly by the mother achieving much better control of her diabetes mellitus prior to conception.

Vascular limb defects and maternal age.

BACKGROUND: The prenatal diagnosis procedure chorionic villus sampling is associated with increased risk of vascular disruption limb defects. Some studies have suggested that these defects are more common among infants born to women 35 years and older while other studies have shown a correlation with younger mothers. METHODS: All infants with vascular disruption defects were identified in the Active Malformations Surveillance Program at Brigham and Women's Hospital in the years 1972-1974, 1979-2011. We compared the rate of occurrence of infants with vascular limb defects among women in theses age groups: ≤19, 20 to 34, and ≥35 years to the rate of occurrence of infants with preaxial polydactyly, adjusting for race. Infants with an identifiable cause of their defects were excluded. RESULTS: 106 infants with vascular disruption defects and 67 with preaxial polydactyly were identified. Seventeen percent of the infants with vascular disruption defects and 25% of the infants with preaxial polydactyly were born to women 35 and older (p = 0.23). In contrast, 16% of the infants with vascular disruption defects were born to young mothers (≤19 years) compared with 6.0% of the mothers of infants with preaxial polydactyly (adjusted odds ratio vs. 35+ years = 5.3, 95% confidence interval 1.4-21, p = 0.017). CONCLUSION: Women 35 years old or older did not have increased risk for having a child with vascular disruption defects, but these defects were more common among infants of young (≤19) mothers, compared with the preaxial polydactyly group.