A new biometric: In utero growth curves for metacarpal and phalangeal lengths reveal an embryonic patterning ratio.

OBJECTIVES: The objectives of this study are to develop gestational age-specific growth curves for fetal third metacarpal and phalangeal lengths and to determine if fetal hand proportion is established in utero. METHODS: This prospective cross-sectional study used 2D ultrasound across gestational ages 12 to 39 weeks to evaluate the third fetal metacarpal and phalangeal measurements. Gestational age-specific reference growth curves were developed. Associations between continuous variables were assessed using Spearman correlations (rs ) and restricted cubic splines. A nonlinear biologic regression model was used to predict metacarpal and phalangeal lengths as a function of gestational age. Measurements derived from five cases of thanatophoric dysplasia were used to determine if brachydactyly could be objectified. RESULTS: Fetal metacarpal and phalangeal lengths are highly correlated across gestational age (rs  = 0.96, P < 0.001). The mean fetal metacarpal to phalangeal ratio is constant from gestational age 15 to 39 weeks (rs  = -0.07, P = 0.49). Third-digit metacarpal and phalangeal lengths in thanatophoric dysplasia showed brachydactyly in all cases (5/5), and none of the cases (0/5) demonstrated a normal metacarpal to phalangeal ratio of 0.49. CONCLUSION: We present gestational age-specific reference growth curves for fetal third metacarpal and phalangeal lengths, which may be used to detect brachydactyly. We demonstrate a prenatal metacarpal to phalangeal ratio of 1:2.

A computational model for the joint onset and development.

Joints connect the skeletal components and enable movement. The appearance and development of articulations is due to different genetic, biochemical, and mechanical factors. In the embryonic stage, controlled biochemical processes are critical for organized growth. We developed a computational model, which predicts the appearance, location, and development of joints in the embryonic stage. Biochemical events are modeled with reaction diffusion equations with generic molecules representing molecules that 1) determine the site where the articulation will appear, 2) promote proliferation, and matrix synthesis, and 3) define articular cartilage. Our model accounts for cell differentiation from mesenchymal cells to pre-cartilaginous cells, then cartilaginous cells, and lastly articular cartilage. These reaction-diffusion equations were solved using the finite elements method. From a mesenchymal 'bud' of a phalanx, the model predicts growth, joint cleavage, joint morphology, and articular cartilage formation. Our prediction of the gene expression during development agrees with molecular expression profiles of joint development reported in literature. Our computational model suggests that initial rudiment dimensions affect diffusion profiles result in Turing patterns that dictate sites of cleavage thereby determining the number of joints in a rudiment.

Altered developmental events in the anterior region of the chick forelimb give rise to avian-specific digit loss.

BACKGROUND: Avian forelimb (wing) contains only three digits, and the three-digit formation in the bird forelimb is one of the avian-specific limb characteristics that have been evolutionarily inherited from the common ancestral form in dinosaurs. Despite many studies on digit formation in the chick limb bud, the developmental mechanisms giving rise to the three-digit forelimb in birds have not been completely clarified. RESULTS: To identify which cell populations of the early limb bud contribute to digit formation in the late limb bud, fate maps of the early fore- and hindlimb buds were prepared. Based on these fate maps, we found that the digit-forming region in the forelimb bud is narrower than that in the hindlimb bud, suggesting that some developmental mechanisms on the anterior-most region lead to a reduced number of digits in the forelimb. We also found temporal differences in the onset of appearance of the ANZ (anterior necrotic zone) as well as differences in the position of the anterior edge of the AER. CONCLUSIONS: Forelimb-specific events in the anterior limb bud are possible developmental mechanisms that might generate the different cell fates in the fore- and hindlimb buds, regulating the number of digits in birds.

Early-to-mid gestation fetal testosterone increases right hand 2D:4D finger length ratio in polycystic ovary syndrome-like monkeys.

A smaller length ratio for the second relative to the fourth finger (2D:4D) is repeatedly associated with fetal male-typical testosterone (T) and is implicated as a biomarker for a variety of traits and susceptibility to a number of diseases, but no experimental human studies have been performed. The present study utilizes the rhesus monkey, a close relative of humans, and employs discrete gestational exposure of female monkeys to fetal male-typical T levels for 15-35 days during early-to-mid (40-76 days; n = 7) or late (94-139 days; n = 7) gestation (term: 165 days) by daily subcutaneous injection of their dams with 10 mg T propionate. Such gestational exposures are known to enhance male-typical behavior. In this study, compared to control females (n = 19), only early-to-mid gestation T exposure virilizes female external genitalia while increasing 2D:4D ratio in the right hand (RH) by male-like elongation of RH2D. RH2D length and 2D:4D positively correlate with androgen-dependent anogenital distance (AG), and RH2D and AG positively correlate with duration of early-to-mid gestation T exposure. Male monkeys (n = 9) exhibit a sexually dimorphic 2D:4D in the right foot, but this trait is not emulated by early-to-mid or late gestation T exposed females. X-ray determined phalanx measurements indicate elongated finger and toe phalanx length in males, but no other phalanx-related differences. Discrete T exposure during early-to-mid gestation in female rhesus monkeys thus appears to increase RH2D:4D through right-side biased, non-skeletal tissue growth. As variation in timing and duration of gestational T exposure alter male-like dimensions of RH2D independently of RH4D, postnatal RH2D:4D provides a complex biomarker for fetal T exposure.

Sonographic visualization of the middle phalanx of the fetal fifth digit between 13 and 17 weeks of gestation.

OBJECTIVE: To assess in utero visualization of the middle phalanx of the fifth digit (MPFD) between 13 and 17 weeks of gestation. METHODS: This was a prospective cross-sectional study in which women attending for fetal sonographic examination between 13 + 0 and 17 + 6 weeks of gestation were evaluated for the presence of the middle phalanx of the fifth digit (MPFD). A total of 682 fetuses with normal findings on first-trimester anatomical examination were recruited. Using transvaginal multifrequency 4-8 and 5-9 MHz probes, the fifth finger was examined in both axial and lateral views until optimal visualization of the MPFD was achieved. RESULTS: The MPFD was visualized in 14.3% (2/14) of cases at 13 weeks, 70.3% (154/219) at 14 weeks, 82.2% (240/292) at 15 weeks, 97.4% (111/114) at 16 weeks and 100% (43/43) at 17 weeks of gestation. CONCLUSIONS: Ultrasound visualization of the MPFD gradually increases during the 13- to 17-week period. This emphasizes the limited role of non-ossification of the MPFD as a sonographic marker of Down syndrome before 17 weeks of gestation.