The Genetic Approach to Hypotonia in the Neonate

Numerous genetic syndromes present with hypotonia during the neonatal period, including Prader-Willi syndrome, myotonic dystrophy, spinal muscular atrophy, congenital muscular dystrophies, nemaline myopathy, congenital hypomyelinating neuropathy, congenital disorders of glycosylation, and Pompe disease. This article reviews neonatal presentations and appropriate diagnostic tests and examinations for each. Awareness of possible underlying genetic causes for neonatal hypotonia can aid physicians in general pediatric practice, neonatology, and other specialties in making a timely diagnosis for what may be considered rare conditions. Furthermore, early diagnosis allows for improved management of affected infants while providing invaluable information to their families with respect to potential recurrence risks in future generations. Introduction Hypotonia is defined as a subjective decrease of resistance to passive range of motion in a newborn (Fig. 1). Knowledge of genetic disorders that present most commonly with hypotonia during the immediate newborn period is imperative because early diagnosis and initiation of appropriate supportive therapies allows the most beneficial outcomes for affected individuals. Molecular testing for most of these disorders is a rapid, cost-effective diagnostic approach. Most molecular tests involve acquiring a modest amount of blood, which is significantly less invasive and more cost effective than prior practices of obtaining muscle via surgical biopsy for similar diagnostic purposes. Prader-Willi Syndrome (PWS) Prenatal hypotonia is evident with PWS, resulting in decreased fetal movement as well as abnormal positioning (ie, breech) at parturition, which causes difficulty with delivery, often necessitating cesarean section. Delivery typically is at term, with normal birth length and weight, although early failure to thrive may result in both parameters falling below the third percentile. During the immediate neonatal period, infants exhibit profound central hypotonia, lethargy, decreased spontaneous movement, and weak cry. Hypogonadism is a common feature; cryptorchidism is present in 80% to 90% of affected males. Characteristic facial features of PWS in the newborn period include dolichocephaly with narrowed bifrontal diameter, “almond-shaped” palpebral *Department of Pediatrics, Division of Medical Genetics, Stanford University School of Medicine, Stanford, Calif. Abbreviations CDG: congenital disorder of glycosylation CHN: congenital hypomyelinating neuropathy