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Seckel syndrome 7(SCKL7)

MedGen UID:
766784
Concept ID:
C3553870
Disease or Syndrome
Synonym: SCKL7
 
Gene (location): NIN (14q22.1)
 
Monarch Initiative: MONDO:0013922
OMIM®: 614851
Orphanet: ORPHA319675

Definition

Microcephalic primordial dwarfism, Dauber type is a rare, genetic developmental defect during embryogenesis characterized by severe pre- and postnatal growth retardation, severe microcephaly, severe developmental delay and intelletual disability, severe adult short stature and facial dysmorphism (incl. hypotelorism, small ears, prominent nose). Other reported features include skeletal anomalies (Madelung deformity, clinodactyly, mild lumbar scoliosis, bilateral hip dysplasia) and seizures. Absence of thelarche and menarche is also associated. [from ORDO]

Clinical features

From HPO
Primary amenorrhea
MedGen UID:
115918
Concept ID:
C0232939
Disease or Syndrome
Abnormally late or absent menarche in a female with normal secondary sexual characteristics.
Uterine hypoplasia
MedGen UID:
120575
Concept ID:
C0266399
Congenital Abnormality
Underdevelopment of the uterus.
Madelung deformity
MedGen UID:
57537
Concept ID:
C0152441
Congenital Abnormality
An anomaly related to partial closure, or failure of development of the ulnar side of the distal radial growth plate, which results in an arrest of epiphyseal growth of the medial and volar portions of the distal radius. This leads to shortening of the radius and relative overgrowth of the ulna.
Short middle phalanx of the 5th finger
MedGen UID:
322335
Concept ID:
C1834060
Anatomical Abnormality
Hypoplastic/small middle phalanx of the fifth finger.
Abnormal carpal morphology
MedGen UID:
374491
Concept ID:
C1840535
Anatomical Abnormality
An abnormality affecting the carpal bones of the wrist (scaphoid, lunate, triquetral, pisiform, trapezium, trapezoid, capitate, hamate).
Clinodactyly of the 5th finger
MedGen UID:
340456
Concept ID:
C1850049
Congenital Abnormality
Clinodactyly refers to a bending or curvature of the fifth finger in the radial direction (i.e., towards the 4th finger).
Severe short stature
MedGen UID:
3931
Concept ID:
C0013336
Disease or Syndrome
A severe degree of short stature, more than -4 SD from the mean corrected for age and sex.
Fetal growth restriction
MedGen UID:
4693
Concept ID:
C0015934
Pathologic Function
An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.
Microtia
MedGen UID:
57535
Concept ID:
C0152423
Congenital Abnormality
Underdevelopment of the external 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.
Intellectual disability, severe
MedGen UID:
48638
Concept ID:
C0036857
Mental or Behavioral Dysfunction
Severe mental retardation is defined as an intelligence quotient (IQ) in the range of 20-34.
Severe global developmental delay
MedGen UID:
332436
Concept ID:
C1837397
Finding
A severe delay in the achievement of motor or mental milestones in the domains of development of a child.
Delayed skeletal maturation
MedGen UID:
108148
Concept ID:
C0541764
Finding
A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.
Lumbar scoliosis
MedGen UID:
412568
Concept ID:
C2748518
Finding
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Developmental dysplasia of the hip
MedGen UID:
1640560
Concept ID:
C4551649
Congenital Abnormality
Congenital dysplasia of the hip (CDH) is an abnormality of the seating of the femoral head in the acetabulum. Its severity ranges from mild instability of the femoral head with slight capsular laxity, through moderate lateral displacement of the femoral head, without loss of contact of the head with the acetabulum, up to complete dislocation of the femoral head from the acetabulum. It is one of the most common skeletal congenital anomalies (summary by Sollazzo et al., 2000). Acetabular dysplasia is an idiopathic, localized developmental dysplasia of the hip that is characterized by a shallow hip socket and decreased coverage of the femoral head. Its radiologic criteria include the center-edge angle of Wiberg, the Sharp angle, and the acetabular roof obliquity. Most patients with acetabular dysplasia develop osteoarthritis (165720) after midlife, and even mild acetabular dysplasia can cause hip osteoarthritis (summary by Mabuchi et al., 2006). CDH occurs as an isolated anomaly or with more general disorders represented by several syndromes and with chromosomal abnormalities such as trisomy 18 (Wynne-Davies, 1970). Genetic Heterogeneity of Developmental Dysplasia of the Hip Developmental dysplasia of the hip-1 (DDH1) maps to chromosome 13q22; DDH2 (615612) maps to chromosome 3p21. DDH3 (620690) is caused by mutation in the LRP1 gene (107770) on chromosome 12q13.
Prominent nose
MedGen UID:
98423
Concept ID:
C0426415
Finding
Distance between subnasale and pronasale more than two standard deviations above the mean, or alternatively, an apparently increased anterior protrusion of the nasal tip.
Central hypothyroidism
MedGen UID:
488836
Concept ID:
C0271801
Disease or Syndrome
A type of hypothyroidism due to an insufficient stimulation of an otherwise normal thyroid gland. Central hypothyroidism is caused by either pituitary (secondary hypothyroidism) or hypothalamic (tertiary hypothyroidism) defects.
Hypotelorism
MedGen UID:
96107
Concept ID:
C0424711
Finding
Interpupillary distance less than 2 SD below the mean (alternatively, the appearance of an decreased interpupillary distance or closely spaced eyes).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVSeckel syndrome 7
Follow this link to review classifications for Seckel syndrome 7 in Orphanet.

Professional guidelines

PubMed

Faienza MF, Acquafredda A, D'Aniello M, Soldano L, Marzano F, Ventura A, Cavallo L
J Pediatr Endocrinol Metab 2013;26(7-8):771-4. doi: 10.1515/jpem-2012-0397. PMID: 23612698
Birkebaek NH, Wolthers OD, Heuch C, Balslev T, Flyvbjerg A, Frystyk J
J Pediatr Endocrinol Metab 2011;24(11-12):995-1000. doi: 10.1515/jpem.2011.369. PMID: 22308854

Recent clinical studies

Etiology

Nerakh G, Vineeth VS, Tallapaka K, Nair L, Dalal A, Aggarwal S
Am J Med Genet A 2022 Jul;188(7):2139-2146. Epub 2022 Mar 17 doi: 10.1002/ajmg.a.62725. PMID: 35298084
Trimouille A, Lasseaux E, Barat P, Deiller C, Drunat S, Rooryck C, Arveiler B, Lacombe D
Clin Genet 2018 Feb;93(2):374-377. Epub 2017 Sep 29 doi: 10.1111/cge.13074. PMID: 28617965
Boisvert RA, Howlett NG
Cell Cycle 2014;13(19):2999-3015. doi: 10.4161/15384101.2014.956475. PMID: 25486561Free PMC Article
Rahme R, Crevier L, Dubois J, Mercier C
Childs Nerv Syst 2010 Jul;26(7):983-6. doi: 10.1007/s00381-010-1142-x. PMID: 20393849
Jacquemont S, Bocéno M, Rival JM, Méchinaud F, David A
Am J Med Genet 2002 Apr 15;109(1):17-21; discussion 16. doi: 10.1002/ajmg.10281. PMID: 11932988

Diagnosis

Smits DJ, Schot R, Popescu CA, Dias KR, Ades L, Briere LC, Sweetser DA, Kushima I, Aleksic B, Khan S, Karageorgou V, Ordonez N, Sleutels FJGT, van der Kaay DCM, Van Mol C, Van Esch H, Bertoli-Avella AM, Roscioli T, Mancini GMS
Hum Genet 2023 Jul;142(7):949-964. Epub 2023 May 17 doi: 10.1007/s00439-023-02569-7. PMID: 37198333Free PMC Article
Pekkola Pacheco N, Pettersson M, Lindstrand A, Grigelioniene G
Am J Med Genet A 2023 Jul;191(7):1929-1934. Epub 2023 Apr 5 doi: 10.1002/ajmg.a.63200. PMID: 37017437
Khojah O, Alamoudi S, Aldawsari N, Babgi M, Lary A
Childs Nerv Syst 2021 Dec;37(12):3847-3860. Epub 2021 Aug 3 doi: 10.1007/s00381-021-05284-8. PMID: 34345934Free PMC Article
Jung M, Rai A, Wang L, Puttmann K, Kukreja K, Koh CJ
Urology 2018 Oct;120:241-243. Epub 2018 Jun 9 doi: 10.1016/j.urology.2018.05.023. PMID: 29894776
Qvist P, Huertas P, Jimeno S, Nyegaard M, Hassan MJ, Jackson SP, Børglum AD
PLoS Genet 2011 Oct;7(10):e1002310. Epub 2011 Oct 6 doi: 10.1371/journal.pgen.1002310. PMID: 21998596Free PMC Article

Therapy

Faienza MF, Acquafredda A, D'Aniello M, Soldano L, Marzano F, Ventura A, Cavallo L
J Pediatr Endocrinol Metab 2013;26(7-8):771-4. doi: 10.1515/jpem-2012-0397. PMID: 23612698
Birkebaek NH, Wolthers OD, Heuch C, Balslev T, Flyvbjerg A, Frystyk J
J Pediatr Endocrinol Metab 2011;24(11-12):995-1000. doi: 10.1515/jpem.2011.369. PMID: 22308854
Ducos B, Cabrol S, Houang M, Perin L, Holzenberger M, Le Bouc Y
J Clin Endocrinol Metab 2001 Nov;86(11):5516-24. doi: 10.1210/jcem.86.11.7985. PMID: 11701730
Hayani A, Suarez CR, Molnar Z, LeBeau M, Godwin J
J Med Genet 1994 Feb;31(2):148-9. doi: 10.1136/jmg.31.2.148. PMID: 8182723Free PMC Article

Prognosis

Batool T, Irshad S, Riaz M, Mahmood Baig S, Nuernberg P, Hussain MS
J Hum Genet 2023 Jul;68(7):469-475. Epub 2023 Mar 3 doi: 10.1038/s10038-023-01132-6. PMID: 36864288
Unal S, Alanay Y, Cetin M, Boduroglu K, Utine E, Cormier-Daire V, Huber C, Ozsurekci Y, Kilic E, Simsek Kiper OP, Gumruk F
Pediatr Blood Cancer 2014 Feb;61(2):302-5. Epub 2013 Sep 17 doi: 10.1002/pbc.24783. PMID: 24106199
Jacquemont S, Bocéno M, Rival JM, Méchinaud F, David A
Am J Med Genet 2002 Apr 15;109(1):17-21; discussion 16. doi: 10.1002/ajmg.10281. PMID: 11932988

Clinical prediction guides

Smits DJ, Schot R, Popescu CA, Dias KR, Ades L, Briere LC, Sweetser DA, Kushima I, Aleksic B, Khan S, Karageorgou V, Ordonez N, Sleutels FJGT, van der Kaay DCM, Van Mol C, Van Esch H, Bertoli-Avella AM, Roscioli T, Mancini GMS
Hum Genet 2023 Jul;142(7):949-964. Epub 2023 May 17 doi: 10.1007/s00439-023-02569-7. PMID: 37198333Free PMC Article
Batool T, Irshad S, Riaz M, Mahmood Baig S, Nuernberg P, Hussain MS
J Hum Genet 2023 Jul;68(7):469-475. Epub 2023 Mar 3 doi: 10.1038/s10038-023-01132-6. PMID: 36864288
Birkebaek NH, Wolthers OD, Heuch C, Balslev T, Flyvbjerg A, Frystyk J
J Pediatr Endocrinol Metab 2011;24(11-12):995-1000. doi: 10.1515/jpem.2011.369. PMID: 22308854
Qvist P, Huertas P, Jimeno S, Nyegaard M, Hassan MJ, Jackson SP, Børglum AD
PLoS Genet 2011 Oct;7(10):e1002310. Epub 2011 Oct 6 doi: 10.1371/journal.pgen.1002310. PMID: 21998596Free PMC Article
Alderton GK, Galbiati L, Griffith E, Surinya KH, Neitzel H, Jackson AP, Jeggo PA, O'Driscoll M
Nat Cell Biol 2006 Jul;8(7):725-33. Epub 2006 Jun 18 doi: 10.1038/ncb1431. PMID: 16783362

Recent systematic reviews

Khojah O, Alamoudi S, Aldawsari N, Babgi M, Lary A
Childs Nerv Syst 2021 Dec;37(12):3847-3860. Epub 2021 Aug 3 doi: 10.1007/s00381-021-05284-8. PMID: 34345934Free PMC Article

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