Emeline Renard

Germline gain of function variations in the AKT3 gene cause brain overgrowth syndrome with megalencephaly and diffuse bilateral cortical malformations. Here we report a child with megalencephaly, who is a carrier of a novel heterozygous missense variant in the AKT3 gene NM_005465.7:c.964G>T,p.Asp322Tyr. The phenotype of this patient is associated with pituitary deficiencies diagnosed at 2 years of age: growth hormone (GH) deficiency responsible for growth delay and central hypothyroidism. After 6 months of GH treatment, intracranial hypertension was noted, confirmed by the observation of papilledema and increased intracranial pressure, requiring the initiation of acetazolamide treatment and the discontinuation of GH treatment. This is the second reported patient described with megalencephaly and AKT3 gene variant associated with GH deficiency . Other endocrine disorders have also been reported in few cases with hypothyroidism and hypoglycemia. Pituitary deficiency may be a part of the of megalencephaly phenotype secondary to germline variant in the AKT3 gene. Special attention should be paid to growth in these patients and search for endocrine deficiency is necessary in case of growth retardation or hypoglycemia.

Objective To evaluate the impact of antenatal corticosteroid therapy (ACS) on birth outcomes in term infants exposed during pregnancy. Study design Exposed newborns were compared with non-exposed controls in a 1 to 2 design. Multivariate analysis was used to assess the effect of ACS exposure on neonatal outcomes. Result 408 newborns were included (136 exposed to ACS, 272 non-exposed). Mean ± SD head circumference (HC) was 33.7 ± 1.4 vs 34.3 ± 1.6 cm, p = 0.001 in exposed vs controls; birth weight was 3.1 ± 0.4 vs 3.3 ± 0.4 kg, p = 0.0001; and birth height was 47.9 ± 2.1 vs. 49.1 ± 2.0 cm, p < 0.0001. Hypocalcemia (4.4 vs 0.7%, p = 0.019) and feeding difficulties (5.1 vs 1.5%, p = 0.047) were significantly more common in exposed newborns. Multivariate analysis for HC showed a significant independent association with ACS exposure (β = −0.5, p = 0.009). Conclusion Term newborns exposed to ACS have lower birth HC and higher risk of neonatal complications. Clinical trial registration NCT05640596.

Objective: To evaluate the impact of antenatal corticosteroid therapy (ACS) on birth parameters of full-term newborns exposed during pregnancy for prematurity threat. Study Design: Exposed newborns were randomly compared to non-exposed controls in a 1-to-2 design. Data were retrospectively collected in infants’ files. Multivariate analysis assessed the impact of ACS on neonatal outcome. Result: 408 term born neonates were included, 136exposed to ACScompared to 272 non-exposed controls. Mean+/-SD Head Circumference (HC) was 33.7+/-1.4 vs 34.3+/-1.6 cm, p=0.001in exposed vs controls; birth weight (BW) 3.1+/-0.4 vs.3.3+/-0.4 Kg; p = 0.0001; Birth Height (BH) 47.9+/-2.1 vs. 49.1+/-2.0 cm; pConclusion: Term neonates exposed to ACS have a smaller HC at birth and a higher risk of neonatal complications.