Diaphragmatic defects and limb deficiencies—Taking sides

Abstract

Diaphragmatic defects and limb deficiencies usually occur as independent anomalies, as a polytopic field defect (in which ipsilateral anomalies might be expected) or as wider pattern of defects, potentially involving disturbance of laterality or the midline (in which bilateral or contralateral defects would occur). Data on cases from previous studies and/or the literature were used to determine whether there is an association between the sides involved in the defects. The 88 adequately described cases identified included 20 with de Lange syndrome, seven with Poland anomaly, four with trisomy 18, 52 with other patterns of multiple malformations and five with diaphragmatic and limb defects alone. Evaluation of the position of the limb (left, right, bilateral) and the diaphragmatic defects (left, right, bilateral) did not show significant association in patterns of sidedness (P = 0.48). In 56% of cases, the limb deficiencies were bilateral. Among the 32 unilateral cases, 19 (59%) were ipsilateral (15 left; 4 right) and 13(41%) were contralateral (P = 0.38). Eleven of the 13 contralateral cases had left sided diaphragmatic defects and right sided limb deficiency; four had de Lange syndrome and nine had other patterns of multiple anomalies. Only cases with Poland anomaly or otherwise isolated defects showed a trend towards ipsilateral defects. Most cases with multiple congenital anomalies, had limbs defects on both the right and left (57%) or both sides of the diaphragm were affected (an additional 10%), indicating a widespread dysmorphogenetic process rather than a more restricted field defect. In other cases, defects were bilateral or, if unilateral, reflected the propensities for diaphragmatic defects to more often involve the left side, and limb defects, the right.

EFNB2haploinsufficiency causes a syndromic neurodevelopmental disorder

“…ARM occurs in defined genetic syndromes and multiple congenital anomalies, such as VACTERL association that was reported in 2 patients with 13qter deletion . Urogenital or anorectal abnormalities associated with deletion 13q are rare; in males, anomalies varies from anal atresia with hypospadias and perineal fistula to distal hypospadias without anorectal abnormalities; in females anal atresia with vaginal fistula has been reported . Our data confirm that EFNB2 could be involved in syndromic forms of anorectal and genitourinary malformations which could explain why no variant in EFNB2 gene were identified in 331 patients with isolated anorectal malformations or in patients with persistent cloaca associated with renal malformations …”

“…EFNB2 has been suggested as a strong candidate gene for hypospadias and/or anorectal malformations (ARM) in 13q deletion syndrome . The spectrum of ARM ranges from simple sphincter abnormalities to complex cloacal malformations.…”

“…EFNB2 has been suggested as a strong candidate gene for hypospadias and/or anorectal malformations (ARM) in 13q deletion syndrome. 6,[28][29][30][31] The spectrum of ARM ranges from simple sphincter abnormalities to complex cloacal malformations. ARM occurs in defined genetic syndromes and multiple congenital anomalies, such as VACTERL association that was reported in 2 patients with 13qter deletion.…”

Characterization of limb differences in children with Cornelia de Lange Syndrome

“…Congenital diaphragmatic hernia (CDH) has also been studied as a prototype of a birth defect that demonstrates laterality. Left‐sided CDH are more common in isolated instances [Torfs et al, ; Enns et al, ; Rosano et al, ; Evans, ]. Slavotinek et al looked at the frequency of R‐sided versus L‐CDH concurrently with the presence of other anomalies.…”

Diagnóstico prenatal de inversión pericentrica del cromosoma cinco de novo en una paciente con gestación a término sin complicaciones posteriores

“…(7). Fuera de esto, existe una variante que son las inversiones de novo que pueden generar severos efectos fenotípicos en el individuo, si el punto de inversión involucra regiones genéticas críticas, entre esas las más comunes son el retardo mental, anormalidades craneofaciales, atresia del meato auditivo y microtia según la región que se afecte (10). Dentro de la secuencia de genes que se codifican en el cromosoma 5, se pueden observar diversas patologías asociadas a las inversiones, entre las que se encuentra el síndrome hipereosinofílico (inversión pericéntrica), que consiste en una entidad rara en la que se evidencia un conteo absoluto de eosinófilos de más de 15.000uL por mas de 6 meses asociado a daño de órgano, eosinofilia reactiva, cánceres hematológicos o fascitis eosinofílica.…”