Pallister-Hall syndrome

O que é Pallister-Hall syndrome?

É uma genética rara síndromes que pode afetar várias partes do corpo, mas especialmente os dedos das mãos e dos pés. É uma condição muito rara, tanto que sua prevalência é desconhecida.

este síndromes também é conhecido como:
Ano - cerebro - digital síndromes Ano-cerebro-digital síndromes Síndrome anocerebrodigital Multiplex de letalidade precoce cerebro-acro-visceral (CAVE) síndromes CerebroAcroVisceralEarlylethalityCAVEmultiplexsyndrome Epilepsia - hamartoblastoma hipotalâmico gelástico síndromes Hamartoblastoma hipotalâmico, hipopituitarismo, ânus imperfurado e polidactilia pós-axial Hipotalâmico-hamartoblastoma síndromes Síndrome hipotálamo-hamartoblastoma

Quais mudanças genéticas causam Pallister-Hall syndrome?

Alterações no gene GLI3 são responsáveis por causar a síndromes.

É herdado em um padrão autossômico dominante.

Quais são os principais sintomas de Pallister-Hall syndrome?

O principal sintomas do síndromes envolvem os dedos das mãos e dos pés. Isso inclui a fusão dos dígitos e a presença de dedos das mãos e pés extras.

O hamartoma hipotálamo, que é um tumor no cérebro, é comum com o síndromes. Geralmente, esses crescimentos não causam problemas médicos. Às vezes, eles podem causar convulsões ou anormalidades hormonais que podem ser fatais na infância.

Outro sintomas incluem epiglote bífida (via aérea malformada), abertura anal obstruída e problemas renais.

Na maioria dos casos, o sintomas característica disso síndromes não são graves.

Possíveis traços / características clínicas:
Rim ectópico, Braquidactilia, Luxação do quadril, Duplicação uretral distal, Encurtamento distal dos membros, Criptorrquidismo, Tamanho testicular diminuído, Fenda lábio superior, Fenda palatina, Atresia do canal auditivo externo, Sindactilia dos dedos, Hipopituitarismo anterior, Hipocortisolemia, Hipocortisolemia, Hipocortisolemia Comprometimento cognitivo, Deficiência de hormônio do crescimento, Baixa estatura, Hemivértebra, Holoprosencefalia, Ponte nasal deprimida, Hamartoma hipotalâmico, Curto 4 o metacarpo, Panhipopituitarismo, Sindactilia do dedo do pé, Persistência do canal arterial, Herança autossômica dominante, Convulsão, Puberdade renal precoce, cisto, Displasia renal, Polidactilia pós-axial da mão, Polidactilia pós-axial do pé, Hipoplasia renal, Nariz curto, dente natal, Narinas antevertidas, Retardo do crescimento intrauterino, implantação baixa, orelhas giradas posteriormente, Displasia renal multicística, Microglossia, Micrognatia, Microtia, Capilaridade facial hemangioma, Micromelia, Micropenis, Microftalmia, Fenda laríngea, Abnorma lobação pulmonar

Como alguém faz o teste de Pallister-Hall syndrome?

O teste inicial para Pallister-Hall syndrome pode começar com a triagem de análise facial, por meio do FDNA Telehealth plataforma telegenética, que pode identificar os principais marcadores do síndromes e delineia a necessidade de mais testes. Seguirá uma consulta com um conselheiro genético e, em seguida, um geneticista. 

Com base nesta consulta clínica com um geneticista, as diferentes opções para testes genéticos serão compartilhadas e o consentimento será solicitado para testes adicionais.

Informações médicas sobre Pallister-Hall syndrome

The four main components of this syndrome are an imperforate anus, post-axial or characteristically mesoaxial polydactyly, hypopituitarism, and an unusual hypothalamic tumour. About 50% of cases have a cleft larynx or bifid epiglottis, although this may be asymptomatic (Ondrey et al., 2000). Stoll et al., (2002) reported a case with stenosis of the cricoid cartilage. Most infants have died because of the untreated pituitary problem. However, see the familial, autosomal dominant cases (below) and the case of Minns et al., (1994) who had gelastic epilepsy and precocious puberty at the age of 3 1/2 years. Verloes et al., (1995) reported two surviving cases (aged 2 and 17 years). These authors emphasised the specific radiological features of the hands and feet which included generalised brachydactyly, severe brachytelephalangism, and proximal synostosis between central metacarpals or meso-axial polydactyly. Biesecker and Graham (1996) provide a good review. Bowing of the radius and ulna and fibula hypoplasia can also occur (Roscioli et al., 2006).
The cerebral tumour is composed of undifferentiated germinal cells and has been called a hamartoblastoma. It is sometimes difficult to detect on a CAT scan, and very thin cuts might be necessary. The infants are small at birth, and males will usually have evidence of hypogonadism. It should be noted that the polydactyly might be unilateral, and the nails might be hypoplastic. Facially the nasal bridge is flat, the nose is short and the ears are posteriorly rotated. Sama et al., (1994) point out that choanal atresia may be part of the spectrum. In females Kaufman-McKusick syndrome must be excluded. In fact Unsinn et al., (1995) reported a case with hypothalamic hamartoblastoma, where hydrocolpos was also present. Galasso et al. (2001) presented a case with growth hormone neurosecretory dysfunction which was successfully treated with growth hormone.
A severe case was reported by McPherson and Cold (2013) that included bilateral absence of the kidneys, a duplicated uterusand a pit in the centre of the philtrum
Most cases have been sporadic, but Graham et al., (1986) reported a patient whose maternal aunt apparently had similar features. Thomas et al., (1994) reported two affected sibs with the condition. The father had nearly complete 4-5 cutaneous syndactyly of the right hand and postaxial polydactyly of both hands. Incomplete dominant inheritance, or mosaicism for a dominant gene in the father was postulated. Topf et al., (1993) reported an affected 9-year-old boy and his 34-year-old father. The boy had precocious puberty. The father had no neurological or endocrinological symptoms in spite of the presence of a large tumour with pituitary dysplasia. Low et al., (1995) reported a mother and son with relatively mild features of the condition and suggested that this mild phenotype can run in families. A similarly mildly affected dominant family was reported by Grebe and Clericuzio. Sills et al., (1993) reported two affected sibs. The surviving sib had pituitary and hypothalamic insufficiency. Subsequently, a third affected child was detected prenatally by ultrasound (Sills et al., 1994). Penman Splitt et al., (1994) reported a mother and two children with the condition. The daughter had full manifestations of the condition whereas the mother had polydactyly, acromesomelic shortening of all limbs, hypoplastic nails, a bifid epiglottis and she was educationally subnormal. There were no apparent endocrine abnormalities. A son born whilst the paper was going to press had polydactyly, syndactyly, anal stenosis, micropenis, but no evidence of hypopituitarism. Cianfarani et al., (1995) reported a case with imperforate anus, bilateral hydronephrosis and anterior pituitary hypoplasia, but no polydactyly or hypothalamic hamartoma. Total colonic aganglionosis and an imperforate anus have also been described (Li et al., 2015).
Hingorani et al., (1991) reported twin fetuses with hypothalamic hamartomas, preaxial polydactyly of the toes (in one), a midline cleft lip, oral frenula, a notched tongue and short long bones. The fourth ventricle was dilated and the cerebellum hypoplastic with an absent inferior vermis. There was a 'keyhole' defect of the foramen magnum. The authors pointed out the overlap with Pallister-Hall syndrome, oro-facio-digital syndromes and hydrolethalus syndrome. Sharma et al., (1993) considered the fetuses reported by Hingorani et al. to have short rib-polydactyly syndrome type IV (Beemer-Langer syndrome). Further confusion was introduced by Encha-Razavi et al., (1992) who reported three cases with hypothalamic hamartomas. One case had a skeletal dysplasia with short and broad long bones with irregular metaphyses and mild curvature of the radii and ulnae, short and broad phalanges, short ribs and narrow cervical vertebrae but no polydactyly (no radiographs were published). There was a midline cleft of the upper lip and oral frenula and a sib was similarly affected. The second case appeared to fall into the Mohr-Majewski spectrum and the third into the Meckel spectrum (with a posterior encephalocele and 'renal dysplasia').
The overall message of the above unusual cases, is that hypothalamic hamartomas appear to be part of several different syndromes, and do not necessarily establish the diagnosis of Pallister-Hall syndrome when seen. Verloes et al., (1992) make this point. They describe a case with holoprosencephaly, hypothalamic hamartoblastoma, Hirschsprung disease and tetramelic postaxial polydactyly. They reiterate the overlap between Pallister-Hall syndrome, Smith-Lemli-Opitz syndrome type II, holoprosencephaly-polydactyly (Young-Madders syndrome), oral-facial-digital syndrome type VI (Varadi-Papp syndrome), and hydrolethalus syndrome. They suggest that many cases overlap and fall into a multiplex phenotype group. Verloes (1995) expands on this concept. Fujiwara et al., (1999) also report a patient with a hypothalamic hamartoma with features of an oral-facial-digital syndrome. Apparently Biesecker has found a Gli3 mutation in that patient (Toriello, 2001 - personal communication).
A patient reported by Sener (1994) with imperforate anus, mesoaxial polydactyly and postaxial oligodactyly of one foot, and a sacral meningocele may well have Pallister-Hall syndrome. The other conditions referred to in this paper most likely represent early descriptions of VATER syndrome. In view of the extreme variability of the syndrome, the family reported by McClay et al., (1997) where various individuals manifested polydactyly and bifid epiglottis, may well represent Pallister-Hall syndrome. Killoran et al., (2000) studied a dominant family with polydactyly, imperforate anus and vertebral anomalies, similar to cases reported by Say and Gerald (1968). A mutation in the GLI3 gene was demonstrated. The authors stress the overlap between VACTERL and Pallister-Hall syndromes.McCann et al., (2006) stress the overlap with Kauman-McKusick syndrome
GENETICS
Kuller et al., (1992) reported a case with an unbalanced karyotype (46,XY,-7,+der(7), t(3;7)(p25.3;q36)pat). Radhakrishna et al., (1999) studied GLI3 mutations in Pallister-Hall syndrome, Greig cepalopolynsyndactyly, and polydactyly type A, and could find no clear genotype/phenotype correlation. Kang et al., (1997) reported mutations in the GLI3 gene at 7p13. Frameshift mutations were demonstrated in two families. Biesecker et al., (1997) provide a good review of the range mutations found in GLI3 in Pallister-Hall syndrome, Greig syndrome, and polydactyly type A. Kang et al., (1997) provide good review of linkage data to 7p13 as well as a clinical review of the condition.
Villavicencio et al., (2000) provide a good review of the Sonic hedgehog-patched-Gli pathway. Johnston et al., (2003) studied 34 patients and identified deletions in 11. Nine patients with deletions had mental retardation or developmental delay. There was clinical overlap with the acrocallosal syndrome. The deletion breakpoints were analyzed in six patients and the size ranged from 151 kb to 10.6 Mb. Greig syndrome is caused by many types of chromosomal alteration, including, translocations, large deletions, exonic deletions, small in-frame deletions, duplications, missense and frameshift/nonsense and splicing mutations. (Johnston et al., 2005). But, according to these authors, Pallister-Hall is caused only by frameshift/nonsense mutations. And, more interestingly, mutations in the first third of the gene cause Greig and mutations in the second third cause Pallister-Hall. There were 12 mutations in the 3 prime end causing Greig, but no Pallister-Hall patients had mutations in this region.

* This information is courtesy of the L M D.
If you find a mistake or would like to contribute additional information, please email us at: [email protected]

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