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Schinzel-Giedion syndrome(SGS)

MedGen UID:
120517
Concept ID:
C0265227
Disease or Syndrome
Synonyms: Schinzel-Giedion midface retraction syndrome; SGS
SNOMED CT: Schinzel-Giedion syndrome (18899000)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Gene (location): SETBP1 (18q12.3)
 
Monarch Initiative: MONDO:0010010
OMIM®: 269150
Orphanet: ORPHA798

Definition

Schinzel-Giedion syndrome is a highly recognizable syndrome characterized by severe mental retardation, distinctive facial features, and multiple congenital malformations including skeletal abnormalities, genitourinary and renal malformations, and cardiac defects, as well as a higher-than-normal prevalence of tumors, notably neuroepithelial neoplasia (summary by Hoischen et al., 2010). [from OMIM]

Additional description

From MedlinePlus Genetics
Schinzel-Giedion syndrome is a severe condition that is apparent at birth and affects many body systems. Signs and symptoms of this condition include distinctive facial features, neurological problems, and organ and bone abnormalities. Because of their serious health problems, most affected individuals do not survive past childhood.

Children with Schinzel-Giedion syndrome can have a variety of distinctive features. In most affected individuals, the middle of the face looks as though it has been drawn inward (midface retraction). Other facial features include a large or bulging forehead; wide-set eyes (ocular hypertelorism); a short, upturned nose; and a wide mouth with a large tongue (macroglossia). Affected individuals can have other distinctive features, including larger than normal gaps between the bones of the skull in infants (fontanelles), a short neck, low-set ears, and an inability to secrete tears (alacrima). Babies with Schinzel-Giedion syndrome often have excessive hairiness (hypertrichosis) that usually disappears in infancy.

Children with Schinzel-Giedion syndrome have severe developmental delay. Other neurological problems can include severe feeding problems, seizures, or visual or hearing impairment. They may also experience short pauses in breathing during sleep (sleep apnea).

Affected individuals can also have abnormalities of organs such as the heart, kidneys, or genitals. Heart defects include problems with the heart valves, which control blood flow in the heart; the chambers of the heart that pump blood to the body (ventricles); or the dividing wall between the sides of the heart (the septum). Most children with Schinzel-Giedion syndrome have an accumulation of urine in the kidneys (hydronephrosis), which can occur in one or both kidneys. Affected individuals can have genital abnormalities such as underdevelopment (hypoplasia) of the genitals. Affected boys may have the opening of the urethra on the underside of the penis (hypospadias).

Bone abnormalities are common in people with Schinzel-Giedion syndrome. The bones at the base of the skull are often abnormally hard or thick (sclerotic), or the joint between the bones at the base of the skull (occipital synchondrosis) can be abnormally wide. In addition, affected individuals may have broad ribs, abnormal collarbones (clavicles), inward- and upward-turning feet (clubfeet), or shortened bones in the arms or legs or at the ends of the fingers (hypoplastic distal phalanges).

Children with Schinzel-Giedion syndrome who survive past infancy have a higher than normal risk of developing certain types of brain tumors called neuroepithelial tumors.  https://medlineplus.gov/genetics/condition/schinzel-giedion-syndrome

Clinical features

From HPO
Teratoma
MedGen UID:
21097
Concept ID:
C0039538
Neoplastic Process
The presence of a teratoma.
Hepatoblastoma
MedGen UID:
61644
Concept ID:
C0206624
Neoplastic Process
A kind of neoplasm of the liver that originates from immature liver precursor cells and macroscopically is composed of tissue resembling fetal or mature liver cells or bile ducts.
Sacrococcygeal teratoma
MedGen UID:
107852
Concept ID:
C0559459
Neoplastic Process
A teratoma arising in the sacro-coccygeal region.
Hydronephrosis
MedGen UID:
42531
Concept ID:
C0020295
Disease or Syndrome
Severe distention of the kidney with dilation of the renal pelvis and calices.
Bicornuate uterus
MedGen UID:
78599
Concept ID:
C0266387
Congenital Abnormality
The presence of a bicornuate uterus.
Small scrotum
MedGen UID:
141577
Concept ID:
C0455792
Finding
Apparently small scrotum for age.
Ureteral stenosis
MedGen UID:
105481
Concept ID:
C0521618
Anatomical Abnormality
The presence of a stenotic, i.e., constricted ureter.
Hydroureter
MedGen UID:
101073
Concept ID:
C0521620
Anatomical Abnormality
The distention of the ureter with urine.
Hypoplastic labia majora
MedGen UID:
107566
Concept ID:
C0566899
Finding
Undergrowth of the outer labia.
Hypospadias
MedGen UID:
163083
Concept ID:
C0848558
Congenital Abnormality
Abnormal position of urethral meatus on the ventral penile shaft (underside) characterized by displacement of the urethral meatus from the tip of the glans penis to the ventral surface of the penis, scrotum, or perineum.
Hypoplastic labia minora
MedGen UID:
376558
Concept ID:
C1849295
Finding
Micropenis
MedGen UID:
1633603
Concept ID:
C4551492
Congenital Abnormality
Abnormally small penis. At birth, the normal penis is about 3 cm (stretched length from pubic tubercle to tip of penis) with micropenis less than 2.0-2.5 cm.
Clubfoot
MedGen UID:
3130
Concept ID:
C0009081
Congenital Abnormality
Clubfoot is a congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities (Cardy et al., 2007). Clubfoot may occur in isolation or as part of a syndrome (e.g., diastrophic dysplasia, 222600). Clubfoot has been reported with deficiency of long bones and mirror-image polydactyly (Gurnett et al., 2008; Klopocki et al., 2012).
Single transverse palmar crease
MedGen UID:
96108
Concept ID:
C0424731
Finding
The distal and proximal transverse palmar creases are merged into a single transverse palmar crease.
Postaxial hand polydactyly
MedGen UID:
609221
Concept ID:
C0431904
Congenital Abnormality
Supernumerary digits located at the ulnar side of the hand (that is, on the side with the fifth finger).
Tibial bowing
MedGen UID:
332360
Concept ID:
C1837081
Finding
A bending or abnormal curvature of the tibia.
Short distal phalanx of finger
MedGen UID:
326590
Concept ID:
C1839829
Finding
Short distance from the end of the finger to the most distal interphalangeal crease or the distal interphalangeal joint flexion point. That is, hypoplasia of one or more of the distal phalanx of finger.
Wide distal femoral metaphysis
MedGen UID:
376560
Concept ID:
C1849309
Finding
Increased width of the distal part of the shaft (metaphysis) of the femur.
Short 1st metacarpal
MedGen UID:
376561
Concept ID:
C1849311
Finding
A developmental defect characterized by reduced length of the first metacarpal (long bone) of the hand.
Atrial septal defect
MedGen UID:
6753
Concept ID:
C0018817
Congenital Abnormality
Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.
Postnatal growth retardation
MedGen UID:
395343
Concept ID:
C1859778
Finding
Slow or limited growth after birth.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Opisthotonus
MedGen UID:
56246
Concept ID:
C0151818
Sign or Symptom
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Hypsarrhythmia
MedGen UID:
195766
Concept ID:
C0684276
Finding
Hypsarrhythmia is abnormal interictal high amplitude waves and a background of irregular spikes. There is continuous (during wakefulness), high-amplitude (>200 Hz), generalized polymorphic slowing with no organized background and multifocal spikes demonstrated by electroencephalography (EEG).
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Long clavicles
MedGen UID:
96530
Concept ID:
C0426808
Finding
Increased length of the clavicles.
Short sternum
MedGen UID:
108394
Concept ID:
C0575497
Finding
Decreased inferosuperior length of the sternum.
Hypoplasia of first ribs
MedGen UID:
331732
Concept ID:
C1834386
Congenital Abnormality
Thickened cortex of long bones
MedGen UID:
333557
Concept ID:
C1840418
Finding
Abnormal thickening of the cortex of long bones.
Broad ribs
MedGen UID:
336390
Concept ID:
C1848654
Finding
Increased width of ribs
Widely patent fontanelles and sutures
MedGen UID:
336570
Concept ID:
C1849300
Finding
An abnormally increased width of the cranial fontanelles and sutures.
Aplasia/Hypoplasia of the pubic bone
MedGen UID:
338651
Concept ID:
C1849305
Finding
Absence or underdevelopment of the pubic bone.
Increased density of long bones
MedGen UID:
340289
Concept ID:
C1849307
Finding
An abnormal increase in the bone density of the long bones.
Sclerosis of skull base
MedGen UID:
377095
Concept ID:
C1851714
Finding
Increased bone density of the skull base without significant changes in bony contour.
Malar flattening
MedGen UID:
347616
Concept ID:
C1858085
Finding
Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.
Shallow orbits
MedGen UID:
351328
Concept ID:
C1865244
Finding
Reduced depth of the orbits associated with prominent-appearing ocular globes.
Wormian bones
MedGen UID:
766814
Concept ID:
C3553900
Congenital Abnormality
The presence of extra bones within a cranial suture. Wormian bones are irregular isolated bones which appear in addition to the usual centers of ossification of the cranium.
Metopic suture patent to nasal root
MedGen UID:
870735
Concept ID:
C4025189
Anatomical Abnormality
The frontal suture divides the two halves of the frontal bone in infants and usually fuses by the age of six years. The suture runs from the bregma (the point on the skull at which the coronal suture is intersected perpendicularly by the sagittal suture) to the nasion or nasal root. This term applies if the suture is widely patent from bregma to nasal root.
Abnormal nasopharynx morphology
MedGen UID:
871265
Concept ID:
C4025750
Anatomical Abnormality
A structural anomaly of the nasopharynx.
Splenopancreatic fusion
MedGen UID:
1706964
Concept ID:
C5139112
Anatomical Abnormality
Fusion of the pancreatic tail and spleen.
Macroglossia
MedGen UID:
44236
Concept ID:
C0024421
Disease or Syndrome
Increased length and width of the tongue.
High forehead
MedGen UID:
65991
Concept ID:
C0239676
Finding
An abnormally increased height of the forehead.
Short neck
MedGen UID:
99267
Concept ID:
C0521525
Finding
Diminished length of the neck.
Choanal stenosis
MedGen UID:
108427
Concept ID:
C0584837
Finding
Abnormal narrowing of the choana (the posterior nasal aperture).
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Prominent forehead
MedGen UID:
373291
Concept ID:
C1837260
Finding
Forward prominence of the entire forehead, due to protrusion of the frontal bone.
Anteverted nares
MedGen UID:
326648
Concept ID:
C1840077
Finding
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
Coarse facial features
MedGen UID:
335284
Concept ID:
C1845847
Finding
Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.
Midface retrusion
MedGen UID:
339938
Concept ID:
C1853242
Anatomical Abnormality
Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle.
Short nose
MedGen UID:
343052
Concept ID:
C1854114
Finding
Distance from nasion to subnasale more than two standard deviations below the mean, or alternatively, an apparently decreased length from the nasal root to the nasal tip.
Sloping forehead
MedGen UID:
346640
Concept ID:
C1857679
Finding
Inclination of the anterior surface of the forehead from the vertical more than two standard deviations above the mean (objective); or apparently excessive posterior sloping of the forehead in a lateral view.
Facial hemangioma
MedGen UID:
348361
Concept ID:
C1861443
Finding
Hemangioma, a benign tumor of the vascular endothelial cells, occurring in the face.
Hypertrichosis
MedGen UID:
43787
Concept ID:
C0020555
Disease or Syndrome
Hypertrichosis is increased hair growth that is abnormal in quantity or location.
Hyperconvex nail
MedGen UID:
488894
Concept ID:
C0423807
Finding
When viewed on end (with the digit tip pointing toward the examiner's eye) the curve of the nail forms a tighter curve of convexity.
Hypoplastic nipples
MedGen UID:
98156
Concept ID:
C0432355
Congenital Abnormality
Underdevelopment of the nipple.
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVSchinzel-Giedion syndrome
Follow this link to review classifications for Schinzel-Giedion syndrome in Orphanet.

Professional guidelines

PubMed

Zhou Y, Quan Y, Wu Y, Zhang Y
J Int Med Res 2022 Sep;50(9):3000605221121955. doi: 10.1177/03000605221121955. PMID: 36113068Free PMC Article

Recent clinical studies

Etiology

Leone MP, Palumbo P, Palumbo O, Di Muro E, Chetta M, Laforgia N, Resta N, Stella A, Castellana S, Mazza T, Castori M, Carella M, Bukvic N
Ital J Pediatr 2020 May 27;46(1):74. doi: 10.1186/s13052-020-00839-y. PMID: 32460883Free PMC Article
Villani A, Greer MC, Kalish JM, Nakagawara A, Nathanson KL, Pajtler KW, Pfister SM, Walsh MF, Wasserman JD, Zelley K, Kratz CP
Clin Cancer Res 2017 Jun 15;23(12):e83-e90. doi: 10.1158/1078-0432.CCR-17-0631. PMID: 28620009
Acuna-Hidalgo R, Deriziotis P, Steehouwer M, Gilissen C, Graham SA, van Dam S, Hoover-Fong J, Telegrafi AB, Destree A, Smigiel R, Lambie LA, Kayserili H, Altunoglu U, Lapi E, Uzielli ML, Aracena M, Nur BG, Mihci E, Moreira LM, Borges Ferreira V, Horovitz DD, da Rocha KM, Jezela-Stanek A, Brooks AS, Reutter H, Cohen JS, Fatemi A, Smitka M, Grebe TA, Di Donato N, Deshpande C, Vandersteen A, Marques Lourenço C, Dufke A, Rossier E, Andre G, Baumer A, Spencer C, McGaughran J, Franke L, Veltman JA, De Vries BB, Schinzel A, Fisher SE, Hoischen A, van Bon BW
PLoS Genet 2017 Mar;13(3):e1006683. Epub 2017 Mar 27 doi: 10.1371/journal.pgen.1006683. PMID: 28346496Free PMC Article
Filges I, Shimojima K, Okamoto N, Röthlisberger B, Weber P, Huber AR, Nishizawa T, Datta AN, Miny P, Yamamoto T
J Med Genet 2011 Feb;48(2):117-22. Epub 2010 Oct 30 doi: 10.1136/jmg.2010.084582. PMID: 21037274
Sandri A, Manazza AD, Bertin D, Silengo M, Basso ME, Forni M, Madon E
J Pediatr Hematol Oncol 2003 Jul;25(7):558-61. doi: 10.1097/00043426-200307000-00012. PMID: 12847324

Diagnosis

Liu WL, He ZX, Li F, Ai R, Ma HW
J Genet 2018 Mar;97(1):35-46. PMID: 29666323
Touge H, Fujinaga T, Okuda M, Aoshi H
Int J Urol 2001 May;8(5):237-41. doi: 10.1046/j.1442-2042.2001.00291.x. PMID: 11328425
Okamoto N, Takeuchi M, Kitajima H, Hosokawa S
Jpn J Hum Genet 1995 Jun;40(2):189-93. doi: 10.1007/BF01883576. PMID: 7662999
Labrune P, Lyonnet S, Zupan V, Imbert MC, Goutieres F, Hubert P, Le Merrer M
Am J Med Genet 1994 Mar 1;50(1):90-3. doi: 10.1002/ajmg.1320500120. PMID: 8160760
Verloes A, Moës D, Palumbo L, Elmer C, François A, Bricteux G
Eur J Pediatr 1993 May;152(5):421-3. doi: 10.1007/BF01955902. PMID: 8319710

Therapy

Miyake F, Kuroda Y, Naruto T, Ohashi I, Takano K, Kurosawa K
J Child Neurol 2015 Jun;30(7):932-6. Epub 2014 Jul 14 doi: 10.1177/0883073814541468. PMID: 25028416
Cooke ME, Davidson LE, Livesey SL
Int J Paediatr Dent 2002 Jan;12(1):66-72. doi: 10.1046/j.0960-7439.2001.00325.x. PMID: 11853250

Prognosis

Kohyanagi N, Ohama T
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Makishima H
Int J Hematol 2017 Jun;105(6):732-742. Epub 2017 Apr 26 doi: 10.1007/s12185-017-2241-1. PMID: 28447248
Albano LM, Sakae PP, Mataloun MM, Leone CR, Bertola DR, Kim CA
Rev Hosp Clin Fac Med Sao Paulo 2004 Apr;59(2):89-92. Epub 2004 Apr 26 doi: 10.1590/s0041-87812004000200008. PMID: 15122424
Sandri A, Manazza AD, Bertin D, Silengo M, Basso ME, Forni M, Madon E
J Pediatr Hematol Oncol 2003 Jul;25(7):558-61. doi: 10.1097/00043426-200307000-00012. PMID: 12847324
Elliott AM, Meagher-Villemure K, Oudjhane K, der Kaloustian VM
Clin Dysmorphol 1996 Apr;5(2):135-42. doi: 10.1097/00019605-199604000-00005. PMID: 8723563

Clinical prediction guides

Kohyanagi N, Ohama T
Genes Cells 2023 Sep;28(9):629-641. Epub 2023 Jul 25 doi: 10.1111/gtc.13057. PMID: 37489294Free PMC Article
Acuna-Hidalgo R, Deriziotis P, Steehouwer M, Gilissen C, Graham SA, van Dam S, Hoover-Fong J, Telegrafi AB, Destree A, Smigiel R, Lambie LA, Kayserili H, Altunoglu U, Lapi E, Uzielli ML, Aracena M, Nur BG, Mihci E, Moreira LM, Borges Ferreira V, Horovitz DD, da Rocha KM, Jezela-Stanek A, Brooks AS, Reutter H, Cohen JS, Fatemi A, Smitka M, Grebe TA, Di Donato N, Deshpande C, Vandersteen A, Marques Lourenço C, Dufke A, Rossier E, Andre G, Baumer A, Spencer C, McGaughran J, Franke L, Veltman JA, De Vries BB, Schinzel A, Fisher SE, Hoischen A, van Bon BW
PLoS Genet 2017 Mar;13(3):e1006683. Epub 2017 Mar 27 doi: 10.1371/journal.pgen.1006683. PMID: 28346496Free PMC Article
Kishimoto K, Kobayashi R, Yonemaru N, Yamamoto H, Tsujioka T, Sano H, Suzuki D, Yasuda K, Suzuki M, Ando A, Tonoki H, Iizuka S, Uetake K, Kobayashi K
J Pediatr Hematol Oncol 2015 May;37(4):e238-41. doi: 10.1097/MPH.0000000000000236. PMID: 25171454
Lehman AM, McFadden D, Pugash D, Sangha K, Gibson WT, Patel MS
Am J Med Genet A 2008 May 15;146A(10):1299-306. doi: 10.1002/ajmg.a.32277. PMID: 18398855

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