|Year : 2018 | Volume
| Issue : 1 | Page : 76-78
Prader–Willi syndrome: A syndromic cause of morbid obesity
Ankur Rawat1, Subhash Chandra Shaw1, Suprita Kalra2, Rakesh Gupta1
1 Department of Pediatrics, Armed Forces Medical College, Pune, Maharashtra, India
2 Department of Pediatrics, Command Hospital, Pune, Maharashtra, India
|Date of Web Publication||9-Jul-2018|
Lt Col Subhash Chandra Shaw
Department of Pediatrics, Armed Forces Medical College, Pune - 411 040, Maharashtra
Source of Support: None, Conflict of Interest: None
Prader–Willi syndrome (PWS) is a complex multisystem genetic disorder with a prevalence of about 1/10,000–1/30,000. It is also the first known disorder of human genomic imprinting. We report a case of a child with PWS presenting with hypotonia and feeding difficulty in the neonatal period and infancy with characteristic facial features, hyperphagia, early onset of morbid obesity, short hands and feet, intellectual disability, and other behavioral problems.
Keywords: Hypogonadism, hypotonia, obesity, Prader–Willi syndrome
|How to cite this article:|
Rawat A, Shaw SC, Kalra S, Gupta R. Prader–Willi syndrome: A syndromic cause of morbid obesity. J Mar Med Soc 2018;20:76-8
| Introduction|| |
Prader–Willi syndrome (PWS), also known as the syndrome of hypotonia–hypomentia–hypogonadism–obesity, is a complex multisystem genetic disorder having great variability in the clinical features during a patient's lifetime. It has a prevalence of about 1/10,000–1/30,000., PWS is the first known disorder of human genomic imprinting, and the characteristic phenotype of this syndrome includes severe hypotonia and feeding difficulty in neonatal period and infancy with characteristic facial features, hyperphagia, early onset of morbid obesity, short stature with short hands and feet, hypogonadism, learning disability, and many other behavioral problems and psychiatric manifestations such as obsessive–compulsive disorder, depression, and excessive preoccupation with food. We report the case of a child with PWS for its complexity of presentation and management and discuss the pertinent review of literature.
| Case Report|| |
A 5-year, 8-month-old female child, the firstborn of a nonconsanguineous marriage, was brought with a history of excessive weight gain since 3 years of age. Antenatal period had been uneventful, including normal fetal movements perceived by mother and normal ultrasound scans. She was born at term by Cesaerean section due to nonprogress of labor. She weighed 2.5 kg at birth and had a weak cry with generalized hypotonia since birth and had a Neonatal Intensive Care Unit stay of about 10 days. Throughout the neonatal period, she was fed by gavage feeding as she remained hypotonic with poor suck. Hypotonia persisted till the 1st year of life. There was developmental delay since early infancy, affecting all developmental domains. Developmental milestones achieved at 5 years were that she could run and was studying in upper kindergarten. After attaining 3 years of age, she developed a voracious appetite with rapid gain in weight. She also had temper tantrums, poor scholastic performance, and extreme insensitivity to any painful stimuli. There was no history of recurrent infections, visual disturbances, chest pain, easy fatigability, breathlessness, recurrent fractures, sleep apnea, or snoring. She looked obese [Figure 1] and weighed 46 kg with body mass index of 35 and both were >+3 Z score (as per the World Health Organization child growth standards). Her height was 114 cm and head circumference was 48 cm, both normal for that age. Her vital parameters were normal and Sexual Maturity Rating (Tanner) was Stage 1. She had dysmorphic features in the form of almond-shaped palpebral fissures, downturned mouth, and thin upper lip [Figure 1]. Both her hands and feet were small [Figure 2]a and [Figure 2]b. Eye evaluation including fundus and hearing evaluation was normal. Her bone age was 7 years and ultrasound sonography pelvis revealed infantile uterus and bilateral ovaries were not visualized. The thyroid function test was normal, but the cortisol level was suboptimal (61.21 nmol/L). Growth hormone (GH) assays were detected to be below the normal range. The MRI brain was normal. Her developmental quotient was 60 and was diagnosed to have mild intellectual disability. Genetic analysis by fluorescence in situ hybridization (FISH) probe LSI SNRPN/LSI PPML/CEP 15 revealed all the metaphases showing deletion in the SNRPN region, which was diagnostic of PWS [Figure 3]. Her parents were counseled and she was advised balanced dietary restriction and regular daily physical activity. She was started on subcutaneous GH injections daily and was advised to add injection hydrocortisone and tablet prednisolone in case of any major illness/surgery.
|Figure 1: Obesity with dysmorphic features of almond-shaped palpebral fissures, downturned mouth|
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|Figure 3: Fluorescence in situ hybridization probe LSI SNRPN/LSI PPML/CEP 15 showing deletion in the SNRPN region|
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| Discussion|| |
PWS was first described in 1956 by Prader et al. The clinical diagnostic criteria of PWS were developed initially through a consensus process in 1993, much before the availability of genetic tests, to help clinicians confirm or rule out the diagnosis on purely clinical basis. Later on, as the diagnostic testing became more and more available worldwide, Gunay-Aygun et al. suggested new criteria that prompt DNA testing for PWS depending on the age group affected. The criteria include hypotonia with poor sucking in children aged less than 2 y, and hypotonia with global developmental delay and poor sucking in those between age of 2 y and 6 y. They include hypotonia, global developmental delay, poor sucking, excessive eating and central obesity in children aged between 6 y and 12 y. Beyond 13 years till adulthood the criteria included excessive eating, central obesity, hypothalamic hypogonadism, cognitive impairment, and/or typical behavioural problems like temper tantrums and obsessive compulsive features. The dysmorphic features described in this disorder matched with our case. These children also have morbid obesity causing advancement of bone age. The PWS region is located on the proximal long arm of chromosome 15 (15q11.2-q13). It is a contiguous gene disorder as the loss of expression of several genes in this region leads to the complete phenotype. The PWS is also a disorder of imprinting, where the expression of relevant genes in 15q11.2-q13 region is paternal in origin. PWS occurs if parental alleles are missing, silenced, or defective. In 70% of cases, there is parental microdeletion of the chromosome 15 q11-q13 (Type I or II depending on the proximal breakpoint). Maternal uniparental disomy accounts for another 25% of cases. The rest of the cases of PWS result either from the translocations of chromosome 15 or genomic imprinting defects (microdeletions or epimutations) of the imprinting center in the 15q11-q13 region. DNA methylation study is considered the most efficient test to diagnose PWS. This is most commonly done using DNA methylation-specific techniques at the SNURF-SNRPN locus. Our case underwent FISH, which showed deletion in the SNRPN region. The management requires multidisciplinary approach as multiple endocrine dysfunction is often associated because of hypothalamic dysfunction. The principles of management of PWS are family education and support and regular exercise, along with strict regulation of the food intake. GH therapy should be started early in the childhood, not only for growth acceleration but also for beneficial effects on body composition (increase in lean body mass and decrease in fat mass), exercise capacity (increase in motor strength), and better cognitive effects. Hypogonadism, hypothyroidism, and adrenal insufficiency need to be addressed and so are the psychological and cognitive issues. As these children grow into adults, quality of life is affected by morbid obesity. The bone mineral density declines during adolescence and adulthood, due to hypogonadism and lower sex hormones during this time. Some authors recommend obtaining annual 25-hydroxy Vitamin D levels for bone health. Death in PWS adults is often related to obesity, due to cardiorespiratory failure or cor pulmonale exacerbated by both central and obstructive sleep apnea, and septicemia due to pneumonias and skin infections. The risk of PWS recurrence in families with affected children is usually <1%, except for translocation-inherited mutation with breakpoint in the 15q11.2-q13 region (recurrence up to 25%) and inherited mutation in the imprinting center (recurrence up to 50%). Temple syndrome (TS14) is another lesser recognized and underdiagnosed imprinting disorder of chromosome 14 which share several clinical features in infancy and childhood with PWS.
| Conclusion|| |
We have presented a case of PWS, the most common syndromic cause of morbid obesity in children. The aim of this case report is to sensitize the readers about the high variability of the clinical features depending on the age of presentation and complexity of multidisciplinary team management.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient's parents have given their consent for images and other clinical information to be reported in the journal. The patient's parents understand that name and initials will not be published.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]