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Schaaf-Yang syndrome(SHFYNG)

MedGen UID:
1807366
Concept ID:
C5575066
Disease or Syndrome
Synonyms: Arthrogryposis, distal, with hypopituitarism, intellectual disability, and facial anomalies; MAGEL2-related Prader-Willi-like syndrome; SHFYNG
SNOMED CT: MAGE family member L2-related Prader-Willi-like syndrome (1229946007); MAGEL2-related Prader-Willi-like syndrome (1229946007); Schaaf Yang syndrome (1229946007)
Modes of inheritance:
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Gene (location): MAGEL2 (15q11.2)
 
Monarch Initiative: MONDO:0014243
OMIM®: 615547
Orphanet: ORPHA398069

Disease characteristics

Excerpted from the GeneReview: Schaaf-Yang Syndrome
Schaaf-Yang syndrome (SYS) is a rare neurodevelopmental disorder that shares multiple clinical features with the genetically related Prader-Willi syndrome. It usually manifests at birth with muscular hypotonia in all and distal joint contractures in a majority of affected individuals. Gastrointestinal/feeding problems are particularly pronounced in infancy and childhood, but can transition to hyperphagia and obesity in adulthood. Respiratory distress is present in many individuals at birth, with approximately half requiring intubation and mechanical ventilation, and approximately 20% requiring tracheostomy. Skeletal manifestations such as joint contractures, scoliosis, and decreased bone mineral density are frequently observed. All affected individuals show developmental delay, resulting in intellectual disability of variable degree, from low-normal intelligence to severe intellectual disability. Other findings may include short stature, seizures, eye anomalies, and hypogonadism. [from GeneReviews]
Authors:
Christian P Schaaf  |  Felix Marbach   view full author information

Clinical features

From HPO
Cryptorchidism
MedGen UID:
8192
Concept ID:
C0010417
Congenital Abnormality
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
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.
Brachydactyly
MedGen UID:
67454
Concept ID:
C0221357
Congenital Abnormality
Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.
Congenital vertical talus
MedGen UID:
66821
Concept ID:
C0240912
Congenital Abnormality
Congenital vertical talus (CVT), also known as 'rocker-bottom foot' deformity, is a dislocation of the talonavicular joint characterized by vertical orientation of the talus with a rigid dorsal dislocation of the navicular, equinus deformity of the calcaneus, abduction deformity of the forefoot, and contracture of the soft tissues of the hind- and mid-foot. This condition is usually associated with multiple other congenital deformities and only rarely is an isolated deformity with familial occurrence (summary by Levinsohn et al., 2004). The condition is transmitted in an autosomal dominant pattern of inheritance, and sometimes shows incomplete penetrance and variable expressivity. There may be a broad spectrum of deformities, including flatfoot, talipes equinovarus (TEV or clubfoot), cavus foot, metatarsus adductus, and even hypoplasia of the tibia (summary by Dobbs et al., 2006).
Tapered finger
MedGen UID:
98098
Concept ID:
C0426886
Finding
The gradual reduction in girth of the finger from proximal to distal.
Small hand
MedGen UID:
108279
Concept ID:
C0575802
Finding
Disproportionately small hand.
Short foot
MedGen UID:
376415
Concept ID:
C1848673
Finding
A measured foot length that is more than 2 SD below the mean for a newborn of 27 - 41 weeks gestation, or foot that is less than the 3rd centile for individuals from birth to 16 years of age (objective). Alternatively, a foot that appears disproportionately short (subjective).
Narrow palm
MedGen UID:
346628
Concept ID:
C1857632
Finding
For children from birth to 4 years of age, the palm width is more than 2 SD below the mean; for children from 4 to 16 years of age the palm width is below the 5th centile; or, the width of the palm appears disproportionately narrow for its length.
Clinodactyly
MedGen UID:
1644094
Concept ID:
C4551485
Congenital Abnormality
An angulation of a digit at an interphalangeal joint in the plane of the palm (finger) or sole (toe).
Obesity
MedGen UID:
18127
Concept ID:
C0028754
Disease or Syndrome
Accumulation of substantial excess body fat.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Failure to thrive in infancy
MedGen UID:
358083
Concept ID:
C1867873
Finding
Constipation
MedGen UID:
1101
Concept ID:
C0009806
Sign or Symptom
Infrequent or difficult evacuation of feces.
Feeding difficulties
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Poor suck
MedGen UID:
324693
Concept ID:
C1837142
Finding
An inadequate sucking reflex, resulting in the difficult of newborns to be breast-fed.
Gastroesophageal reflux
MedGen UID:
1368658
Concept ID:
C4317146
Finding
A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter.
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.
Polyphagia
MedGen UID:
9369
Concept ID:
C0020505
Finding
A neurological anomaly with gross overeating associated with an abnormally strong desire or need to eat.
Impulsivity
MedGen UID:
43850
Concept ID:
C0021125
Mental or Behavioral Dysfunction
Acting on the spur of the moment in response to immediate stimuli; acting on a momentary basis without a plan or consideration of outcomes; having difficulty establishing or following plans; experiencing a sense of urgency and engaging in self-harming behavior when under emotional distress.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Sleep apnea
MedGen UID:
11458
Concept ID:
C0037315
Disease or Syndrome
An intermittent cessation of airflow at the mouth and nose during sleep is known as sleep apnea. Apneas that last at least 10 seconds are considered significant, but individuals with sleep apnea may experience apneas lasting from 20 seconds up to 2 or 3 minutes. Patients may have up to 15 events per hour of sleep.
Delayed ability to walk
MedGen UID:
66034
Concept ID:
C0241726
Finding
A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Inability to walk
MedGen UID:
107860
Concept ID:
C0560046
Finding
Incapability to ambulate.
Autistic behavior
MedGen UID:
163547
Concept ID:
C0856975
Mental or Behavioral Dysfunction
Persistent deficits in social interaction and communication and interaction as well as a markedly restricted repertoire of activity and interest as well as repetitive patterns of behavior.
Skin-picking
MedGen UID:
488979
Concept ID:
C1696701
Mental or Behavioral Dysfunction
Repetitive and compulsive picking of skin which results in tissue damage.
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
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.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Exaggerated anterior convexity of the thoracic vertebral column.
Retrognathia
MedGen UID:
19766
Concept ID:
C0035353
Congenital Abnormality
An abnormality in which the mandible is mislocalised posteriorly.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Camptodactyly
MedGen UID:
195780
Concept ID:
C0685409
Congenital Abnormality
The distal interphalangeal joint and/or the proximal interphalangeal joint of the fingers or toes cannot be extended to 180 degrees by either active or passive extension.
Neonatal hypotonia
MedGen UID:
412209
Concept ID:
C2267233
Disease or Syndrome
Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period.
Arthrogryposis multiplex congenita
MedGen UID:
1830310
Concept ID:
C5779613
Disease or Syndrome
Multiple congenital contractures in different body areas.
Weak cry
MedGen UID:
65892
Concept ID:
C0234860
Finding
Open mouth
MedGen UID:
116104
Concept ID:
C0240379
Finding
A facial appearance characterized by a permanently or nearly permanently opened mouth.
Mandibular prognathia
MedGen UID:
98316
Concept ID:
C0399526
Finding
Abnormal prominence of the chin related to increased length of the mandible.
Short palpebral fissure
MedGen UID:
98067
Concept ID:
C0423112
Finding
Distance between the medial and lateral canthi is more than 2 SD below the mean for age (objective); or, apparently reduced length of the palpebral fissures.
Narrow forehead
MedGen UID:
326956
Concept ID:
C1839758
Finding
Width of the forehead or distance between the frontotemporales is more than two standard deviations below the mean (objective); or apparently narrow intertemporal region (subjective).
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.
Thick eyebrow
MedGen UID:
377914
Concept ID:
C1853487
Finding
Increased density/number and/or increased diameter of eyebrow hairs.
Abnormality of the philtrum
MedGen UID:
384043
Concept ID:
C1857045
Finding
An abnormality of the philtrum.
Decreased fetal movement
MedGen UID:
68618
Concept ID:
C0235659
Finding
An abnormal reduction in quantity or strength of fetal movements.
Fetal akinesia deformation sequence 1
MedGen UID:
220903
Concept ID:
C1276035
Disease or Syndrome
Decreased fetal activity associated with multiple joint contractures, facial anomalies and pulmonary hypoplasia. Ultrasound examination may reveal polyhydramnios, ankylosis, scalp edema, and decreased chest movements (reflecting pulmonary hypoplasia).
Hypogonadism
MedGen UID:
5711
Concept ID:
C0020619
Disease or Syndrome
A decreased functionality of the gonad.
Esotropia
MedGen UID:
4550
Concept ID:
C0014877
Disease or Syndrome
A form of strabismus with one or both eyes turned inward ('crossed') to a relatively severe degree, usually defined as 10 diopters or more.
Myopia
MedGen UID:
44558
Concept ID:
C0027092
Disease or Syndrome
Nearsightedness, also known as myopia, is an eye condition that causes blurry distance vision. People who are nearsighted have more trouble seeing things that are far away (such as when driving) than things that are close up (such as when reading or using a computer). If it is not treated with corrective lenses or surgery, nearsightedness can lead to squinting, eyestrain, headaches, and significant visual impairment.\n\nNearsightedness usually begins in childhood or adolescence. It tends to worsen with age until adulthood, when it may stop getting worse (stabilize). In some people, nearsightedness improves in later adulthood.\n\nFor normal vision, light passes through the clear cornea at the front of the eye and is focused by the lens onto the surface of the retina, which is the lining of the back of the eye that contains light-sensing cells. People who are nearsighted typically have eyeballs that are too long from front to back. As a result, light entering the eye is focused too far forward, in front of the retina instead of on its surface. It is this change that causes distant objects to appear blurry. The longer the eyeball is, the farther forward light rays will be focused and the more severely nearsighted a person will be.\n\nNearsightedness is measured by how powerful a lens must be to correct it. The standard unit of lens power is called a diopter. Negative (minus) powered lenses are used to correct nearsightedness. The more severe a person's nearsightedness, the larger the number of diopters required for correction. In an individual with nearsightedness, one eye may be more nearsighted than the other.\n\nEye doctors often refer to nearsightedness less than -5 or -6 diopters as "common myopia." Nearsightedness of -6 diopters or more is commonly called "high myopia." This distinction is important because high myopia increases a person's risk of developing other eye problems that can lead to permanent vision loss or blindness. These problems include tearing and detachment of the retina, clouding of the lens (cataract), and an eye disease called glaucoma that is usually related to increased pressure within the eye. The risk of these other eye problems increases with the severity of the nearsightedness. The term "pathological myopia" is used to describe cases in which high myopia leads to tissue damage within the eye.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVSchaaf-Yang syndrome

Professional guidelines

PubMed

Juriaans AF, Kerkhof GF, Hokken-Koelega ACS
Endocr Rev 2022 Jan 12;43(1):1-18. doi: 10.1210/endrev/bnab026. PMID: 34460908
Buers I, Persico I, Schöning L, Nitschke Y, Di Rocco M, Loi A, Sahi PK, Utine GE, Bayraktar-Tanyeri B, Zampino G, Crisponi G, Rutsch F, Crisponi L
Clin Genet 2020 Jan;97(1):209-221. Epub 2019 Sep 16 doi: 10.1111/cge.13639. PMID: 31497877
Guo W, Nie Y, Yan Z, Zhu X, Wang Y, Guan S, Kuo Y, Zhang W, Zhi X, Wei Y, Yan L, Qiao J
Sci China Life Sci 2019 Jul;62(7):886-894. Epub 2019 May 30 doi: 10.1007/s11427-019-9541-0. PMID: 31152388

Recent clinical studies

Etiology

Juriaans AF, Kerkhof GF, Hokken-Koelega ACS
Endocr Rev 2022 Jan 12;43(1):1-18. doi: 10.1210/endrev/bnab026. PMID: 34460908
Hebach NR, Caro P, Martin-Giacalone BA, Lupo PJ, Marbach F, Choukair D, Schaaf CP
Clin Genet 2021 Sep;100(3):298-307. Epub 2021 Jun 6 doi: 10.1111/cge.14000. PMID: 34013972
Powell WT, Schaaf CP, Rech ME, Wrede J
Pediatr Pulmonol 2020 Nov;55(11):3162-3167. Epub 2020 Sep 12 doi: 10.1002/ppul.25056. PMID: 32889788
Negishi Y, Ieda D, Hori I, Nozaki Y, Yamagata T, Komaki H, Tohyama J, Nagasaki K, Tada H, Saitoh S
Orphanet J Rare Dis 2019 Dec 2;14(1):277. doi: 10.1186/s13023-019-1249-4. PMID: 31791363Free PMC Article
Gregory LC, Shah P, Sanner JRF, Arancibia M, Hurst J, Jones WD, Spoudeas H, Le Quesne Stabej P, Williams HJ, Ocaka LA, Loureiro C, Martinez-Aguayo A, Dattani MT
J Clin Endocrinol Metab 2019 Dec 1;104(12):5737-5750. doi: 10.1210/jc.2019-00631. PMID: 31504653Free PMC Article

Diagnosis

Juriaans AF, Kerkhof GF, Hokken-Koelega ACS
Endocr Rev 2022 Jan 12;43(1):1-18. doi: 10.1210/endrev/bnab026. PMID: 34460908
Ahn H, Seo GH, Oh A, Lee Y, Keum C, Heo SH, Kim T, Choi J, Kim GH, Ko TS, Yum MS, Lee BH, Choi IH
Medicine (Baltimore) 2020 Dec 18;99(51):e23864. doi: 10.1097/MD.0000000000023864. PMID: 33371171Free PMC Article
Marbach F, Elgizouli M, Rech M, Beygo J, Erger F, Velmans C, Stumpel CTRM, Stegmann APA, Beck-Wödl S, Gillessen-Kaesbach G, Horsthemke B, Schaaf CP, Kuechler A
Orphanet J Rare Dis 2020 Oct 19;15(1):294. doi: 10.1186/s13023-020-01557-8. PMID: 33076953Free PMC Article
Powell WT, Schaaf CP, Rech ME, Wrede J
Pediatr Pulmonol 2020 Nov;55(11):3162-3167. Epub 2020 Sep 12 doi: 10.1002/ppul.25056. PMID: 32889788
Buers I, Persico I, Schöning L, Nitschke Y, Di Rocco M, Loi A, Sahi PK, Utine GE, Bayraktar-Tanyeri B, Zampino G, Crisponi G, Rutsch F, Crisponi L
Clin Genet 2020 Jan;97(1):209-221. Epub 2019 Sep 16 doi: 10.1111/cge.13639. PMID: 31497877

Therapy

Halloun R, Habib C, Ekhilevitch N, Weiss R, Tiosano D, Cohen M
Eur J Med Genet 2021 Aug;64(8):104252. Epub 2021 May 27 doi: 10.1016/j.ejmg.2021.104252. PMID: 34051361
Hebach NR, Caro P, Martin-Giacalone BA, Lupo PJ, Marbach F, Choukair D, Schaaf CP
Clin Genet 2021 Sep;100(3):298-307. Epub 2021 Jun 6 doi: 10.1111/cge.14000. PMID: 34013972

Prognosis

Sanderson MR, Fahlman RP, Wevrick R
J Biol Chem 2021 Aug;297(2):100959. Epub 2021 Jul 12 doi: 10.1016/j.jbc.2021.100959. PMID: 34265304Free PMC Article
Chen X, Ma X, Zou C
Medicine (Baltimore) 2020 Jul 17;99(29):e20574. doi: 10.1097/MD.0000000000020574. PMID: 32702813Free PMC Article
Kleinendorst L, Pi Castán G, Caro-Llopis A, Boon EMJ, van Haelst MM
Am J Med Genet A 2018 Nov;176(11):2456-2459. Epub 2018 Sep 20 doi: 10.1002/ajmg.a.40486. PMID: 30238631
Jobling R, Stavropoulos DJ, Marshall CR, Cytrynbaum C, Axford MM, Londero V, Moalem S, Orr J, Rossignol F, Lopes FD, Gauthier J, Alos N, Rupps R, McKinnon M, Adam S, Nowaczyk MJM, Walker S, Scherer SW, Nassif C, Hamdan FF, Deal CL, Soucy JF, Weksberg R, Macleod P, Michaud JL, Chitayat D
J Med Genet 2018 May;55(5):316-321. Epub 2018 Mar 29 doi: 10.1136/jmedgenet-2017-105222. PMID: 29599419

Clinical prediction guides

Dötsch L, Matesevac L, Strong TV, Schaaf CP
Mol Genet Genomic Med 2023 Dec;11(12):e2262. Epub 2023 Aug 3 doi: 10.1002/mgg3.2262. PMID: 37533374Free PMC Article
Castilla-Vallmanya L, Centeno-Pla M, Serrano M, Franco-Valls H, Martínez-Cabrera R, Prat-Planas A, Rojano E, Ranea JAG, Seoane P, Oliva C, Paredes-Fuentes AJ, Marfany G, Artuch R, Grinberg D, Rabionet R, Balcells S, Urreizti R
J Med Genet 2023 Apr;60(4):406-415. Epub 2022 Sep 7 doi: 10.1136/jmg-2022-108690. PMID: 36243518Free PMC Article
Sanderson MR, Fahlman RP, Wevrick R
J Biol Chem 2021 Aug;297(2):100959. Epub 2021 Jul 12 doi: 10.1016/j.jbc.2021.100959. PMID: 34265304Free PMC Article
Jobling R, Stavropoulos DJ, Marshall CR, Cytrynbaum C, Axford MM, Londero V, Moalem S, Orr J, Rossignol F, Lopes FD, Gauthier J, Alos N, Rupps R, McKinnon M, Adam S, Nowaczyk MJM, Walker S, Scherer SW, Nassif C, Hamdan FF, Deal CL, Soucy JF, Weksberg R, Macleod P, Michaud JL, Chitayat D
J Med Genet 2018 May;55(5):316-321. Epub 2018 Mar 29 doi: 10.1136/jmedgenet-2017-105222. PMID: 29599419
McCarthy JM, McCann-Crosby BM, Rech ME, Yin J, Chen CA, Ali MA, Nguyen HN, Miller JL, Schaaf CP
J Med Genet 2018 May;55(5):307-315. Epub 2018 Mar 1 doi: 10.1136/jmedgenet-2017-105024. PMID: 29496979

Recent systematic reviews

Patak J, Gilfert J, Byler M, Neerukonda V, Thiffault I, Cross L, Amudhavalli S, Pacio-Miguez M, Palomares-Bralo M, Garcia-Minaur S, Santos-Simarro F, Powis Z, Alcaraz W, Tang S, Jurgens J, Barry B, England E, Engle E, Hess J, Lebel RR
Clin Genet 2019 Dec;96(6):493-505. Epub 2019 Aug 22 doi: 10.1111/cge.13620. PMID: 31397880Free PMC Article

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