A 36 week premie infant female is transferred to an academic medical center for persistent hypotonia and poor feeding for one week. She is a dichorionic-diamnionic twin gestation. The pregnancy was complicated by decreased fetal movement, polyhydraminios and amniotic fluid reduction. Chromosomes on the amniontic fluid were normal. Her family history is negative.
She was delivered by cesarean section with Apgar scores of 41 and 85 and had hypotonia and a weak suck by report. She had some apnea without bradycardia on day of life #1 and required nasogastric feedings of breastmilk. She had a normal head CT. Her physical examination upon transfer shows her to be generally emaciated with a weight of 2136 grams, respiratory rate of 48 and shallow breathing, generalized hypotonia with no suck or swallow reflexes. Her gag reflex is normal. Her DTRs are 1+/2+ and are slow to recoil. She has no clonus. The rest of her physical examination is unremarkable.
Her laboratory evaluation includes a normal newborn screening test, TORCH titres, creatinine kinase, T4 and TSH, and electrolytes. Genetic testing for inherited metabolic problems, including a chromosome methylation test, confirms the diagnosis of Prader Willi Syndrome.
Prader Willi is an autosomal dominant genetic syndrome most commonly caused by a paternal deletion on chromosome 15 (~70%). A mneumonic for the clinical syndrome is H3O = hyptonia, hypogonadotropic hypogonadism, hypomentation and obesity.
Patients also often have decreased fetal activity in utero. At birth, patients often have diminished suck and swallowing. Feeding improves by ~ 6 months but from 12-18 months onward there is uncontrolled hyperphagia and decreased linear growth. Patients also often have cryptorchidism with hypoplastic penis and scrotum in boys and hypoplastic labiae in girls. There is normal size of hands and feet in the first year of life which become smaller later in life.
The face is often characterized by strabismus, almond-shaped eyes, triangular mouth and a narrow bifrontal diameter. Plethoric obesity is striking feature. Hypotonia improves with time but the hypomentation becomes more apparent.
The syndrome was first described by Langsdon-Down in 1887 and later by Prader in 1956.
Hypotonia is a common diagnostic problem. It may occur with or without weakness. Decreased fetal movements in utero, persistant hypotonia and difficulty feeding are more consistant with congenital rather than an acquired hypotonia. Common treatable conditions such as hypothyroidism, electrolyte abnormalities and metabolic problems can often be ruled in or out relatively quickly. Supportive treatment while the evaluation progresses is important. The differential diagnosis can be long but often can be identified with an anatomical location:
- Central Nervous System
- Perinatal hypoxia, birth trauma
- Metabolic disorders – mucopolysaccaridosis, lipidoses
- Chromosomal disorders – Down Syndrome
- Spinal Cord
- Spinal cord injury
- Spinal muscle atrophy – Werdnig-Hoffmann
- Neuromuscular Junction
- Congenital myasthenia
- Neonatal myasthenia
- Skeletal muscle
- Congenital muscular dystrophy
- Congenital myotonic dystrophy
- Metabolic myopathies – glycogenoses, mitochondrial
- Structural congenital myopathies – nemaline, central core, myotubular
- Connective Tissue
- Ehler-Dahlos Syndrome
- Marfan Syndrome
- Prader-Willi Syndrome
- Benign Congenital Hypotonia
- Metabolic – hypocalcemia, hypermagnesemia
- Endocrine – hypothyroidism
- Maternal drugs – narcotics near or at time of birth
- Organophosphate intoxication
This patient had persistant hypotonia and difficulty feeding. She also had decreased fetal movements antenatally. Both of these are consistent with a congenital rather than acquired hypotonia and the patient was evaluated accordingly.This patient received aggressive nutritional support during evaluation and after. Her parents also received parental education and were scheduled for a formal genetic counseling session after discharge.
Questions for Further Discussion
1. What are the elements of the physical examination that can help narrow the differential diagnosis?
2. How would nerve conduction or electromyelogram tests be helpful?
3. What follow-up is necessary for a patient with Prader Willi Syndrome?
4. Although each patient and family are different, what are some of the basic tenets of delivering bad news to families?
To Learn More
To view pediatric review articles on this topic from the past year check PubMed.
National Center for Biotechnology Information, U.S. National Library of Medicine. Online Mendelian Inheritance of Man. Prader-Willi Syndrome;PWS. Available from the Internet at: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176270 (rev. 10/14/04, cited 10/18/04)
Rudolph CD, et.al. Rudolph’s Pediatrics 21st edit. McGraw-Hill, New York, NY. 2003. pp. 2303-2304.
Donna M. D’Alessandro, MD
Associate Professor of Pediatrics, Children’s Hospital of Iowa
November 8, 2004