[FONT=&]Two patients exhbiting characteristic facial appearance, including narrow temples, an elongated face, thin upper lip, and a prominent nose[/FONT] [FONT=&]a) a 15-year-old male. b) a 41-year-old female.[/FONT] [FONT=&]Both of them were hypotonic in the neonatal period and showed failure to thrive in the first year and had delayed onset of puberty. Identify the syndrome.[/FONT]
Ans: Prader–Willi syndrome Credit to Dr. Kittychan and Dr. Angela for pinning the diagnosis. Most of us are programmed to identify the plumper version of Prader willi . But this image / typical phenotype takes at least 5 years to develop and if the access to food is limited ( not in proportion to the hunger of Prader willi patients ) or if the parents are very tight about the diet, then the children will not be obese, but will have the other features of the syndrome. Also, as already mentioned these children are not born obese and when faced with a hypotonic newborn - the typical facial features will help rule in / rule out Prader-Willi. Notice the typical facial characteristics[FONT=&] including narrow temples, an elongated face, thin upper lip, and a prominent nose[/FONT]. In summary Prader-Willi is traditionally characterized by hypotonia, short stature, hyperphagia, obesity, behavioral issues (specifically OCD-like behaviors), small hands and feet, hypogonadism, and mild mental retardation.[SUP][/SUP] However, with early diagnosis and early treatment (such as with growth hormone therapy), the prognosis for persons with PWS is beginning to change. Like autism, PWS is a spectrum disorder and so symptoms can range from mild to severe, and may change throughout the person's lifetime. Various organ systems are affected. Early diagnosis of PWS allows for early intervention as well as the early prescription of growth hormone. Daily recombinant growth hormone (GH) injections are indicated for children with PWS. GH supports linear growth and increased muscle mass, and may lessen food preoccupation and weight gain. I hope, this will be a helpful review.
Obesity + Retarded Sexual Development Obesity + Retarded Sexual Development / Infertility - Differentials ( PWS look alikes ) The first and possibly the most common is - Hypothyroidism Others are Albright hereditary osteodystrophy (AHO) is characterized by variable mental retardation, short stature, round face, short neck, short bones of the fingers and toes, calcifications or ossifications in subcutaneous tissues often near joints, delayed development of the adult teeth, enamel hypoplasia (incomplete or underdeveloped tooth enamel), and obesity. Bardet-Biedl syndrome (BBS) is characterized by more toes or fingers than normal at birth, progressive vision loss, renal abnormalities, developmental delay, hypogonadism (lack of sexual development), short to low normal stature, and obesity. Other findings include diabetes mellitus, endocrinological dysfunction, and behavioral abnormalities. Adiposogenital dystrophy is a condition which may be caused by secondary hypogonadism originating from decreased levels in GnRH. Low levels of GnRH has been associated with defects of the feeding centers of the hypothalamus, leading to an increase consumption of food and thus caloric intake. It is characterized by: 1) Feminine obesity 2) Growth retardation and retarded sexual development, atrophy or hypoplasia of the gonads, and altered secondary sex characteristics, 3) headaches 4) Problems with vision 5) polyuria, polydipsia It is usually associated with tumours of the hypothalamus, causing increased appetite and depressed secretion of gonadotropin. It seems to affect males mostly. Alstrom syndrome (AS) produces symptoms in children that include progressive loss of vision and hearing, acanthosis nigricans, short stature, renal failure, dilated or enlarged heart, and obesity. Visual impairment typically begins with photophobia in the first 6 months and advances to blindness by 30 years. Obesity is typically present before 5 years and increases with age. Deafness usually presents late in the first decade, and renal failure often occurs by the third decade. AS is inherited in an autosomal recessive pattern and one gene locus has been found on chromosome 2. Down syndrome is caused by three copies of chromosome 21 and is a highly recognized genetic syndrome. Individuals with Down syndrome can develop obesity stemming from environmental causes such as overeating and lack of exercise. However, several features of Down syndrome can also explain a higher prevalence of obesity. Individuals with Down syndrome can have short stature, hypotonia, and hypothyroidism, all of which increase the likelihood of becoming obese. Turner syndrome - Short stature, broad chest, developmental abnormalities of the heart and large blood vessels, and neck webbing are common characteristics. Growth hormone replacement therapy is becoming common treatment for short stature individuals with Turner syndrome. One very common cause of infertility and obesity among females is PCOS, but sexual development is usually complete. (-:
Related Self Assessment Question [FONT=&] A 6-day-old infant has severe hypotonia and poor feeding since birth. All the syndromes listed below are associated with overweight conditions in children. For the other clinical findings in this patient, select the syndrome with which it is most likely to be associated.[/FONT] [FONT=&]A. Prader-Willi syndrome[/FONT] [FONT=&]B. Laurence-Moon-Biedl syndrome[/FONT] [FONT=&]C. Cushing syndrome[/FONT] [FONT=&]D. Fröhlich syndrome[/FONT] [FONT=&]E. Pseudohypoparathyroidism[/FONT] [FONT=&]F. Polycystic ovary syndrome[/FONT] [FONT=&]G. Type 2 diabetes[/FONT] [FONT=&]EXPLANATION: [/FONT] [FONT=&]Patients with type 2 diabetes mellitus have insulin resistance in their skeletal muscles, increased hepatic glucose production, and decreased insulin secretion in response to elevated levels of glucose. They also develop hyperlipidemia and many complications of chronic hyperglycemia. Acanthosis nigricans, is a common finding in type 2 diabetes.[/FONT] [FONT=&]The Prader-Willi syndrome is a disorder consisting of hypotonia, hypogonadism, hyperphagia after the newborn period, hypomentia, and obesity. A deletion of a portion of chromosome 15 has been found in approximately 70% of patients. Children affected by this syndrome exhibit little movement in utero and are hypotonic during the neonatal period. Feeding difficulties and failure to thrive can be the presenting complaints in the first year; later, obesity becomes the most common presenting complaint. The enormous food intake of affected children is thought to be caused by a defect in the satiety center in the hypothalamus. Stringent caloric restriction is the only known treatment. [/FONT] [FONT=&]Laurence-Moon-Biedl (Bardet-Biedl) syndrome is transmitted as an autosomal recessive trait. Obesity, mental retardation, hypogonadism, polydactyly, and retinitis pigmentosa with night blindness are the principal findings in affected children. There is no known effective treatment. [/FONT] [FONT=&]Fröhlich syndrome, also known as adiposogenital dystrophy, is a rare cause of childhood obesity associated with a hypothalamic tumor.[/FONT] [FONT=&]Pseudohypoparathyroidism is a collective term for a variety of diseases. Affected patients have biochemical findings (low serum calcium and high serum phosphorus levels) similar to those associated with hypoparathyroidism, but they also have high levels of endogenous parathyroid hormone; in addition, exogenous parathyroid hormone fails to increase their phosphate excretion or raise their serum calcium level. The defects in these patients appear to be at the hormone receptor site or in the adenylate cyclase-cyclic AMP system. The symptoms of pseudohypoparathyroidism are caused by hypocalcemia. Affected children are short, round-faced, and mildly retarded. Metacarpals and metatarsals are shortened, and subcutaneous and basal ganglia calcifications as well as cataracts can be present. The current treatment consists of large doses of vitamin D and reduction of the phosphate load.[/FONT] [FONT=&]Polycystic ovary disease classically presents at or shortly after puberty with obesity, hirsutism, and secondary amenorrhea. Later, these women have anovulatory infertility. The cause of this condition is not entirely clear.[/FONT] [FONT=&]The initial complaint in Cushing syndrome may be obesity. Accumulation of fat in the face, neck, and trunk causes the characteristic "buffalo hump" and "moon" facies. Characteristic features include growth failure, muscle wasting, thinning of the skin, plethora, and hypertension. The bone age of affected patients is retarded, and osteoporosis can be present. The disorder results from an excess of glucocorticoids that may be caused by a primary adrenal abnormality (adenoma or carcinoma) or secondary hypercortisolism, which may be owing to excess adrenocorticotropin. Exogenous glucocorticoids administered in supraphysiologic doses for a prolonged period of time will produce a similar picture in normal subjects. [/FONT] [FONT=&]The answer is A. [/FONT]
Another self Assessment Question New discoveries made possible by advances in molecular genetics have broadened our understanding of nontraditional inheritance. Match this disease with the appropriate genetic mechanism: a mentally retarded 4-year-old boy who was noted to be hypotonic at birth and had failure to thrive in infancy now has a tremendous appetite, obesity, hypogonadism, and small hands and feet. A. Mitochondrial inheritance B. Mosaicism C. Genomic imprinting D. Sex chromosome imbalance E. Triplet repeat expansion disorder EXPLANATION: The mitochondrial genome originates only from the ovum and is therefore transmitted by the mother to her offspring of both genders. Mitochondrial disease involves mainly brain and muscle. Ragged red fibers seen on muscle biopsy are present in several inherited enzyme defects. Examples of mitochondrial inheritance include myoclonic epilepsy and ragged red fibers (MERF); mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS); and Leber hereditary optic neuropathy (LHON), a condition not associated with myopathy. Prader-Willi syndrome, which is characterized by hypotonia, obesity, hypogonadism, mental retardation, and characteristic hands, feet, and facies, is caused by a chromosomal deletion of 15q11-13 when the chromosome is of paternal origin. In some syndromes, such as Angelman syndrome, chromosomal deletion of maternal origin results in a syndrome characterized by a specific facies, happy disposition, mental retardation, bizarre movements, and seizures. More recently, cases of Prader-Willi syndrome have been found wherein there is no DNA deletion but both copies of chromosome 15 have been inherited from the mother; similarly, some cases of Angelman syndrome have been shown to have two copies of paternally derived chromosome 15. This suggests that it is the lack of part of paternal chromosome 15 that causes Prader-Willi syndrome and the lack of part of maternal chromosome 15 that causes Angelman syndrome. Some conditions have a more dynamic mutation that can continue to expand with errors in replication. These are called triplet repeat expansion disorders, and include fragile X syndrome, Huntington disease, and myotonic dystrophy. As the gene is further replicated and expanded, protein production ceases and clinical symptoms are expressed. Hypomelanosis of Ito is not thought to be inherited, but does display mosaicism in that about half of affected patients have two distinct cell lines of skin fibroblasts. Other examples of inherited mosaicism include higher functioning patients with trisomy 21, who may display some physical findings consistent with the syndrome but may not have as severe cognitive delay, as some cells have trisomy 21 and others do not. The answer is C.
