European Journal of Obstetrics & Gynecology and Reproductive Biology
Original ArticleBrachmann–de Lange syndrome: a cause of early symmetric fetal growth delay
Introduction
Brachmann–de Lange syndrome (BdLS) is characterized by pre- and postnatal growth delay and mental retardation, microbrachycephaly, hirsutism, visceral and limb anomalies and a characteristic face. Because the diagnosis is entirely based upon phenotypic findings, an extensive catalog of clinical manifestations has been compiled, including confluent eyebrows (synophrys), long curved eyelashes, anteverted nostrils, a long philtrum, thin lips, downturned corners of the mouth, micrognathia, a low-pitched growling voice, flexion contractures and micromelia [1], [2].
The estimated birth prevalence varies from 1 in 10 000 in the United States to 1 in 50 000 in Denmark [3], [4]. There is no sex predominance [5].
The cause of the BdLS is unknown, the majority of cases being sporadic. A de novo autosomal dominant mutation seems to cause the severe form of the disease, recurrence within sibships being explained by germinal mosaicism [6], but in rare families both autosomal dominant and recessive inheritance has been implicated [7], [8], [9]. A striking concordance in monozygotic twins and discordance in dizygotic twins has been reported [3]. If inherited, the mildly affected cases are almost always transmitted by the mother. A considerable phenotypic overlap occurs with duplication 3q syndrome, but Lopez-Rangel [10] emphasized that the critical region for BdLS is located distal to 3q26.1. A similar metabolic abnormality (hyperketosis, ketoaciduria and C6–C12 dicarboxylic aciduria) has been reported in a patient with BdLS and in a patient with Silver–Russell syndrome [11]. Chromosome 9 abnormalities have also been implicated because Pregnancy Associated Placental Protein (PAPP-A) has been described to be absent in the maternal serum and placental tissue of affected infants and PAPP-A maps to chromosome 9 [12]. Until now this syndrome has been diagnosed only five times prior to birth, respectively at 18 weeks gestation (WG) [13], 20 weeks [12], two cases at 32 weeks [14] and one at 34 weeks [15]. Our case is the third one reported during the second trimester.
Section snippets
Case report
A 21-year-old gravida 3, para 1, with unremarkable family history presented for routine ultrasound examination at mid-trimester. She was not related to her husband and had given birth to a healthy child with a normal weight. No pregnancy complication could be detected, neither vascular, nor infectious. A first ultrasonic scan at 10 weeks gestation (WG) was considered to be normal. At 20 WG ultrasound examination demonstrated a fetus with microbrachycephaly (cranial circumference at −2 S.D.) and
Discussion
Patients diagnosed as having BdLS represent a heterogenous group: the most severe variant was first described by Brachmann in 1916 [1] and is characterized by pre- and postnatal growth delay, severe mental retardation, a typical face and major longitudinal limb defects and a milder condition is exemplified by the cases reported by de Lange in 1933 [2], lacking the severe limb defects and showing a variable combination of other major or minor diagnostic manifestations with a better psychomotor
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