Pallister-Hall syndrome is a very rare genetic disorder characterized by polydactyly, nail dysplasia, a bifid epiglottis, and hypothalamic hamartomas producing specific forms of epilepsy. First signs are seen at birth. The prognosis depends on the severity of the disease, ranging from mild to severe and life-threatening. The diagnosis rests on a thorough clinical assessment, followed by imaging studies and molecular genetic testing.
Pallister-Hall syndrome, firstly described 40 years ago, is an extremely rare genetic disorder    . The pathogenesis stems from mutations in the GLI3 gene on chromosome 7p13, which is involved in the sonic hedgehog pathway, a key signaling process of cell maturation   . So far, the majority of cases have been described as familial with an autosomal dominant pattern of inheritance  . The nature of the disorder causes signs and symptoms to be evident from birth. Several key features comprise Pallister-Hall syndrome      :
- Polydactyly - The presence of additional fingers arising from the ulnar/fibular parts of the limbs is a crucial clinical finding in this patient population, often accompanied by dysplasia of the nails .
- Hypothalamic hamartoma - Hamartomas can be quite large (up to several centimeters in length) and produce seizures. The term "gelastic epilepsy" is used to describe a specific type of a partial complex seizure that presents with clonic movements of the diaphragm and chest and mimic laughing . Other neurological deficits, growth hormone deficiency, or even precocious puberty has been attributed to hamartomas, but many patients are surprisingly asymptomatic  . In fact, surgical treatment is often contraindicated due to consequent hypopituitarism and several other complications. In rare patients who develop Pallister-Hall syndrome in a sporadic fashion, deficiency of cortisol might be encountered .
- Bifid epiglottis - In the majority of cases, this anatomical abnormality is asymptomatic, but severe derangements lead to dangerous airway obstruction and death without early treatment  .
Additional signs and symptoms include renal malformation (hypoplasia, agenesis, ectopic kidneys, or development of cysts), genitourinary changes (imperforate anus, hydrometrocolpos), and skeletal changes such as short limbs   .
Entire Body System
- Short Stature
We conclude that children with Pallister-Hall syndrome and short stature be evaluated carefully for spontaneous somatotropic function and, if necessary, treated with growth hormone. [ncbi.nlm.nih.gov]
On examination, he had dysmorphic facies with bulbous nose tip, small stubby hands with central polydactyly and short stature. The MRI of the brain showed a hypothalamic hamartoma. [longdom.org]
Idiopathic short stature (ISS) Idiopathic short stature is characterized by significant short stature ( rd percentile for height will be found to be growth hormone deficient or have mutations involving growth hormone releasing hormone (GHRH), GH, IGF- [hormones.gr]
Growth hormone (GH) deficiency follows; in children, this causes short stature, delayed growth, and delayed puberty. [checkorphan.org]
stature, and intellectual disabilities) 759.89 Rud's (mental deficiency, epilepsy, and infantilism) 759.89 Russell (-Silver) (congenital hemihypertrophy and short stature) 759.89 Seckel's 759.89 sick Silver's (congenital hemihypertrophy and short stature [icd9data.com]
- Dysmorphic Face
face in the form of small ears pointing backwards, small retroverted nose, with flat nasal bridge, vertical groove in the middle of the upper lip philtrum, small tongue, and hypothalamic hamartomas causing hypopituitarism, micropenis, lethargy, hypoglycemia [pediatricneurosciences.com]
- Progressive Mental Retardation
The severe CNS manifestations of these children are reminiscent of children with non-syndromic HH who often have progressive mental retardation with behavioral problems and intractable seizures. [ncbi.nlm.nih.gov]
Because of the very rare occurrence of Pallister-Hall syndrome in general practice, the diagnosis may be difficult to attain. For this reason, an early clinical workup is critical in order to recognize the key elements of this disorder. Physicians should first obtain a detailed patient history that will cover the onset of symptoms and their progression. A detailed family history must not be overlooked because of the autosomal dominant pattern of inheritance. After history taking, the physical examination can discover polydactyly and additional anatomical changes, but in order to solidify the diagnosis and obtain additional evidence toward Pallister-Hall syndrome, imaging studies are necessary. The cardinal feature, hypothalamic hamartoma, is best seen through magnetic resonance imaging (MRI), as neither computed tomography (CT) nor cranial ultrasonography are able to detect it . A non-calcified and non-enhancing mass, usually located behind the optic chiasm and on the third ventricle floor, exhibits an isointense signal on T1 and T2-weighted studies  . Molecular genetic techniques, which are able to detect the mutated GLI3 gene on chromosome 7, serve as the definitive method for diagnosing Pallister-Hall syndrome .
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