Total colonic aganglionosis and imperforate anus in a severely affected infant with Pallister‐Hall syndrome

Li, Mindy H.; Eberhard, Moriah; Mudd, Pamela; Javia, Luv; Zimmerman, Robert F.; Khalek, Nahla; Zackai, Elaine H.

doi:10.1002/ajmg.a.36915

Cited by 10 publications

(8 citation statements)

References 23 publications

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“…[52][53][54] In particular, targeted deletion of Smo in mice as well as Gli1 or Shh overexpression leads to abnormal ENS development. [55][56][57] HSCR has been reported in other ciliopathies or congenital anomalies of Hh-signal transduction, including BBS types 1 and 4-7, 58 JATD, 59 JBTS, 60 and PHS, 61 although the predisposition to HSCR remains low in these disorders. In individual P1, HSCR could have been explained by an additional genetic event at the RET locus in which rare variations and frequent predisposing polymorphisms have been reported.…”

Section: Discussionmentioning

confidence: 99%

Bi-allelic Variations of SMO in Humans Cause a Broad Spectrum of Developmental Anomalies Due to Abnormal Hedgehog Signaling

Sribudiani

Dong

et al. 2020

The American Journal of Human Genetics

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The evolutionarily conserved hedgehog (Hh) pathway is essential for organogenesis and plays critical roles in postnatal tissue maintenance and renewal. A unique feature of the vertebrate Hh pathway is that signal transduction requires the primary cilium (PC) where major pathway components are dynamically enriched. These factors include smoothened (SMO) and patched, which constitute the core reception system for sonic hedgehog (SHH) as well as GLI transcription factors, the key mediators of the pathway. Here, we report biallelic loss-of-function variations in SMO in seven individuals from five independent families; these variations cause a wide phenotypic spectrum of developmental anomalies affecting the brain (hypothalamic hamartoma and microcephaly), heart (atrioventricular septal defect), skeleton (postaxial polydactyly, narrow chest, and shortening of long bones), and enteric nervous system (aganglionosis). Cells derived from affected individuals showed normal ciliogenesis but severely altered Hh-signal transduction as a result of either altered PC trafficking or abnormal activation of the pathway downstream of SMO. In addition, Hh-independent GLI2 accumulation at the PC tip in cells from the affected individuals suggests a potential function of SMO in regulating basal ciliary trafficking of GLI2 when the pathway is off. Thus, loss of SMO function results in abnormal PC dynamics of key components of the Hh signaling pathway and leads to a large continuum of malformations in humans.

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Section: Discussionmentioning

confidence: 99%

Bi-allelic Variations of SMO in Humans Cause a Broad Spectrum of Developmental Anomalies Due to Abnormal Hedgehog Signaling

Sribudiani

Dong

et al. 2020

The American Journal of Human Genetics

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“…Other features in PHS may include abnormal lung lobation, renal abnormalities including cystic malformations, renal hypoplasia, ectopic ureteral implantation, genitourinary anomalies and Hirschsprung's disease. 4 Rarely cochlear anomalies have also been reported, and is usually caused by truncating frame shift/ nonsense and splicing mutations in the middle third of GLI3. 7 The clinical course of the PHS ranges from mild to lethal in the neonatal period.…”

Section: Discussionmentioning

confidence: 99%

Bifid epiglottis with midline laryngeal hamartoma: a rare presentation of Pallister Hall syndrome

Thirunavukkarasu

Sandu²,

Revathy

et al. 2020

Int J Contemp Pediatr

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Bifid epiglottis is a rare laryngeal anomaly that can be an isolated occurrence or as part of malformation syndromes, commonly the Pallister Hall syndrome (PHS). PHS presents with hypothalamic hamartomas, polysyndactyly, bifid epiglottis, imperforate anus and genitourinary abnormalities. We report a case of a 22 months old male child with features of PHS and Hirschsprung's disease. The presentations are with a hypothalamic mass, a bifid epiglottis and a midline mass in the larynx with symptoms of respiratory distress. The laryngeal lesion was endoscopically excised and its histology confirmed as hamartoma (laryngeal). The importance of an early diagnosis of PHS, genetic counselling and prompt management of a compromised airway and endocrine abnormalities is emphasized to have a better outcome.

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“…To date, a total of 12 patients with PHS, including the present patient, have had cardiovascular abnormalities (Table ) . Genital abnormalities were observed in eight patients, renal in six, and gastrointestinal in five.…”

mentioning

confidence: 82%

Critical association of Pallister–Hall syndrome and congenital heart disease

Ochiai¹,

Nagata

Tanaka

et al. 2019

Pediatrics International

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Total colonic aganglionosis and imperforate anus in a severely affected infant with Pallister‐Hall syndrome

Cited by 10 publications

References 23 publications

Bi-allelic Variations of SMO in Humans Cause a Broad Spectrum of Developmental Anomalies Due to Abnormal Hedgehog Signaling

Bi-allelic Variations of SMO in Humans Cause a Broad Spectrum of Developmental Anomalies Due to Abnormal Hedgehog Signaling

Bifid epiglottis with midline laryngeal hamartoma: a rare presentation of Pallister Hall syndrome

Critical association of Pallister–Hall syndrome and congenital heart disease

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