Impact of COVID-19 Pandemic on a Multidisciplinary Approach to Reverse Phenotyping: A Case Report on Prenatal Diagnosis of CAMRQ Type 4 Syndrome

Abstract

Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 4 (CAMRQ4) is a heterogenous group of genetic disorders that have been grouped based on their shared clinical features. CAMRQ4 should be suspected in patients presenting with ataxia, mental retardation, hypotonia, microcephaly, choreoathetoid movements or chorea, ophthalmoplegia, and global developmental delay, even if brain magnetic resonance imaging appears to be normal. We describe a family for whom reverse phenotyping played a crucial role in achieving the correct diagnosis of CAMRQ4 in the index child and prenatal diagnosis for the subsequent pregnancy. We describe the multidisciplinary approach that was followed during the pandemic, ensuring that the family was appropriately guided and informed.

Keywords

SARS-CoV-2 pandemic reverse phenotyping CAMRQ4 syndrome prenatal diagnosis multidisciplinary telehealth approach

Get full access to this article

View all access options for this article.

References

Alsahli

, Alfadhel

Further Delineation of clinical phenotype of Cerebellar Ataxia, Mental Retardation, and Disequilibrium Syndrome type 4 (CAMRQ4); report of 5 new patients and review of previously reported cases. Neurology . 2017;88(16 Supplement):P4.078.

McMillan

, Telegrafi

, Singleton

, Recessive mutations in ATP8A2 cause severe hypotonia, cognitive impairment, hyperkinetic movement disorders and progressive optic atrophy. Orphanet J Rare Dis . 2018;13(1):86.

Onat

, Gulsuner

, Bilguvar

, Missense mutation in the ATPase, aminophospholipid transporter protein ATP8A2 is associated with cerebellar atrophy and quadrupedal locomotion. Eur J Hum Genet . 2013;21(3):281–285.

De Goede

, Yue

, Yan

, Role of reverse phenotyping in interpretation of next generation sequencing data and a review of INPP5E related disorders. Eur J Paediatr Neurol . 2016;20(2):286–295.

Schueller

, Klein

, Tseng

, Covid-19 in India: potential impact of the lockdown and other longer-term policies. https://cddep.org/wp-content/uploads/2020/04/India-Shutdown-Modeling-Slides-Final-2.pdf. Accessed March 9, 2021.

Cacciagli

, Haddad

, Mignon-Ravix

, Disruption of the ATP8A2 gene in a patient with a t(10;13) de novo balanced translocation and a severe neurological phenotype. Eur J Hum Genet . 2010;18(12):1360–1363.

Martín-Hernández

, Rodríguez-García

, Camacho

, New ATP8A2 gene mutations associated with a novel syndrome: encephalopathy, intellectual disability, severe hypotonia, chorea and optic atrophy. Neurogenetics . 2016;17(4):259–263.

Palau

, Espinós

Autosomal recessive cerebellar ataxias. Orphanet J Rare Dis . 2006;1(1):1–19.