Terminal transverse limb defects with “nubbins”

Abstract

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.”

Hypothesis: Central digit hypoplasia

“…His daughter's affected right hand showed a rudimentary thumb and nubbins with small nails in place of fingers 2 to 5, the phenotype of central digit hypoplasia.The active surveillance of almost 300,000 births, including stillbirths and fetuses in pregnancies terminated electively because of anomalies, detected prenatally, has provided an overview of the many, many causes of limb deficiencies. The three phenotypes highlighted in this analysis, central digit hypoplasia, and in two others published separately, describing terminal transverse limb defects(Holmes & Nasri, 2021) and symbrachydactyly, accounted for 25% of the 194 affected fetuses and infants identified. And yet, studies of limb deficiency often do not identify these phenotypes.…”

“…Terminal transverse limb defects (TTLD): These limb defects were at the level of either the proximal forearm, the wrist, or the forefoot but not at the level of the metacarpal–phalangeal joint, the location of central digit hypoplasia. In addition, most of the infants with TTLD have tiny digit‐like nubbins off center at the end of the stump (Gardiner & Holmes, 2012; Holmes & Nasri, 2021). The nubbins in infants with TTLD were smaller than the soft‐tissue nubbins in infants with central digit hypoplasia. Symbrachydactyly: This limb defect occurs in one or both hands or feet (Imagawa, 1980; Uchida et al, 1993).…”

Transverse limb deficiency of the upper extremities

“…However, it is assumed that hypoperfusion disrupts AER development [11]. This can be attributed to vaso-occlusive events and vascular causes like thromboses, vasospasms, and embolisms [12][13][14].…”

“…However, it is assumed that hypoperfusion disrupts AER development 11 . This can be attributed to vaso-occlusive events and vascular causes like thromboses, vasospasms, and embolisms 12 13 14 . Other etiologies include maternal thrombophilia 15 , alpha thalassemia 16 , and cocaine abuse 17 .…”

“…Es wird aber angenommen, dass eine Hypoperfusion zur Disruption der Entwicklung der AER führt 11 . Dies kann auf vasookklusive Ereignisse und vaskuläre Ursachen wie Thrombosen, Vasospasmen und Embolien zurückzuführen sein 12 13 14 . Andere Ätiologien umfassen mütterliche Thrombophilien 15 , Alpha-Thalassämien 16 oder Kokain-Abusus 17 .…”