The clinical relevance of Kagami-Ogata syndrome for neonatal care

With a prevalence of<1:1.000 000, the Kagami-Ogata syndrome (KOS) belongs to the rare genetic disorders [1]. It is most commonly caused by paternal uniparental disomy of the chromosomal region 14q32.3 but also epimutations and maternal microdeletions can occur [2]. The clinical phenotype is coined by the pathognomonic small bell-sharped thorax with coat hanger ribs. Other abnormalities are facial dysmorphism, abdominal wall defects and developmental delay. Neonates often represent with severe respiratory distress and dysphagia [1] [2].

The aim of the study was to evaluate the clinical relevance of KOS for neonatal care and to describe the typical pre- and postnatal symptom constellations.

We reviewed the clinical history of 3 patients with KOS who were treated on the neonatal intensive care unit. All patients had a MEG3 hypermethylation in methylation-sensitive Multiplex Ligation-Depend Probe Amplification (MS-MLPA) so that the diagnosis could be genetically confirmed.

3/3 patients had prenatal abnormalities including polyhydramnion (3/3) and fetometry with estimated weight above the 90th percentile (2/3). Both male patients were suspected of having oesophageal atresia due to a absent fetal stomach bubble and had a thorax hypoplasia. All patients were preterm newborns with a gestational age between 29+5 and 34+5 weeks. A severe respiratory distress requiring an invasive ventilation (3/3). The X-ray showed a small bell-sharped thorax with coat hanger ribs (3/3). Facial dysmorphism (3/3) and short extremities (2/3) were also present. Oesophageal atresia could not be confirmed in any patient, but all of them suffered from a severe dysphagia (3/3). One patient died due to an unclear fulminant metabolic dysfunction with secondary cardiovascular failure when he was just a few hours old. The other 2 children required a neonatal treatment for 95 respectively 134 days. Both children were discharged on high-flow respiratory support.

The severe respiratory distress and dysphagia are of great importance for the postnatal management. Therefore, the aim should be a prenatal diagnosis. The combination of polyhydramnion, absent stomach bubble, thorax hypoplasia and an estimated weight above the 90^th percentile in fetometry should raise awareness to KOS and a specific diagnostic with MS-MLPA should be initiated. The classical prenatal chromosomal diagnostic as well as exome sequencing does not capture KOS. The postnatal pathognomonic picture of a small bell-sharped thorax with coat hanger appearance of the ribs should always be associated with KOS.

Publication History

Article published online:
15 November 2023

• Literature

• 1 Sakaria R.P.. et al Kagami-Ogata Syndrome: Case Series and Review of Literature. AJP reports 2021; 11 (02) e65-e75
• 2 Ogata T., Kagami M.. Kagami-Ogata syndrome: a clinically recognizable upd(14)pat and related disorder affecting the chromosome 14q32.2 imprinted region. Journal of human genetics 2016; 61 (02) 87-94