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J Pediatr Genet 2015; 04(03): 159-167
DOI: 10.1055/s-0035-1564443
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Neurodevelopmental Disorders Associated with Abnormal Gene Dosage: Smith–Magenis and Potocki–Lupski Syndromes

Juanita Neira-Fresneda
1   Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States
,
Lorraine Potocki
1   Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States
2   Texas Children's Hospital, Houston, Texas, United States
› Author Affiliations
Further Information

Publication History

19 June 2015

23 June 2015

Publication Date:
28 September 2015 (online)

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Abstract

Smith–Magenis syndrome (SMS) and Potocki–Lupski syndrome (PTLS) are reciprocal contiguous gene syndromes within the well-characterized 17p11.2 region. Approximately 3.6 Mb microduplication of 17p11.2, known as PTLS, represents the mechanistically predicted homologous recombination reciprocal of the SMS microdeletion, both resulting in multiple congenital anomalies. Mouse model studies have revealed that the retinoic acid–inducible 1 gene (RAI1) within the SMS and PTLS critical genomic interval is the dosage-sensitive gene responsible for the major phenotypic features in these disorders. Even though PTLS and SMS share the same genomic region, clinical manifestations and behavioral issues are distinct and in fact some mirror traits may be on opposite ends of a given phenotypic spectrum. We describe the neurobehavioral phenotypes of SMS and PTLS patients during different life phases as well as clinical guidelines for diagnosis and a multidisciplinary approach once diagnosis is confirmed by array comparative genomic hybridization or RAI1 gene sequencing. The main goal is to increase awareness of these rare disorders because an earlier diagnosis will lead to more timely developmental intervention and medical management which will improve clinical outcome.

Keywords

congenital heart disease - autism - intellectual disability - mirror traits - gene dosage
 

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