Neuropediatrics 2019; 50(S 02): S1-S55
DOI: 10.1055/s-0039-1698271
Poster Presentations
Poster Area GNP Varia 2/Genetics
Georg Thieme Verlag KG Stuttgart · New York

Two Children with Helsmoortel-Van der Aa Syndrome and a Mutation in the ADNP Gene but Variable Clinical Appearance

Nikoletta Nikolaou
1   Vestische Kinder- und Jugendklinik Datteln, Universität Witten/Herdecke, Klinik für Neuropädiatrie, Datteln, Germany
,
Margarete Koch-Hogrebe
1   Vestische Kinder- und Jugendklinik Datteln, Universität Witten/Herdecke, Klinik für Neuropädiatrie, Datteln, Germany
,
Dagmar Wieczorek
2   Universitätsklinikum Düsseldorf, Institut für Humangenetik, Düsseldorf, Germany
,
Claudia Roll
4   Vestische Kinder- und Jugendklinik Datteln, Universität Witten/Herdecke, Klinik für Neonatologie und Pädiatrische Intensivmedizin, Perinatalzentrum, Datteln, Germany
,
Johannes Lemke
,
Kevin Rostasy
1   Vestische Kinder- und Jugendklinik Datteln, Universität Witten/Herdecke, Klinik für Neuropädiatrie, Datteln, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
11 September 2019 (online)

 
 

    Background: Helsmoortel-Van der Aa syndrome is a recently described syndrome of craniofacial dysmorphism, congenital ocular defects and developmental delay associated with mutations in the ADNP gene. Affected individuals have autistic features, mental disabilities, speech and motor developmental delays. A correlation between genotype and phenotype is described in some studies. Here we present two children with the above syndrome, same mutation in the ADNP gene, but a different phenotype.

    Case 1: The first child was presented to us at the age of 9 months for global developmental delay and secondary microcephaly. The child was born in the 38 + 6 weeks by emergency caesarean section. (Weight 2680 g, length 48 cm, head circumference 34 cm, Apgar 10/10, pH 7.24). Due to respiratory problems she was transferred to ICU. She had also problems with swallowing requiring tube feeding. At the age of 5 months, the mother noticed a delaying the development of her child. A head size of 40cm indicated a secondary microcephaly. She was referred to our attention for further work-up including imaging, neurometabolic and chromosomal testing. All tests were normal. Due to the combination of global developmental delay, microcephaly, and facial abnormalities, a microcephaly panel and trio-exome sequencing were performed, which showed a mutation in the ADNP p. Arg730 gene.

    Case 2: The second child was born at 38 + 1 gestation week by caesarean section, because of placenta previa. (weight 3200, length 50 cm, head circumference 38 cm, Apgar 8/10/10, pH 7.29). She was referred on the second day of life because of cyanotic episodes with apnea and muscle spasms. Apart of the macrocephaly facial dysmorphism ( prominent forehead, enophthalmus) and a marked hypotonia. The examinations, including neurometabolic diagnostics, were unremarkable. The MRI skull showed a subdural hematoma and a wide Sylvian fissures on both sides. Heart echo showed signs of pulmonary hypertension. Chromosome analysis was unremarkable. Because of the recurrent episodes, a therapy with clonazepam was started. The Trio-exome sequencing showed the same mutation in the ADNP gene as in the first patient.

    Conclusions: Although the literature suggests a correlation between genotype and phenotype in this rare syndrome, we show that the clinical appearance can be very different. In children with autistic features and ocular abnormalities, this syndrome should be included in the differential diagnosis. Clinical presentation of a complex neurodevelopmental disorder caused by mutations in ADNP

    Reference

    1. AnkeVan Dijck et al. Biological PsychiatryVolume 2019;85(4):287–297


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    No conflict of interest has been declared by the author(s).