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Seckel syndrome 1(SCKL1)

MedGen UID:
1637056
Concept ID:
C4551474
Disease or Syndrome
Synonyms: MICROCEPHALIC PRIMORDIAL DWARFISM I; SCKL1
 
Gene (location): ATR (3q23)
 
Monarch Initiative: MONDO:0008869
OMIM®: 210600

Definition

Seckel syndrome is a rare autosomal recessive disorder characterized by intrauterine growth retardation, dwarfism, microcephaly with mental retardation, and a characteristic 'bird-headed' facial appearance (Shanske et al., 1997). Genetic Heterogeneity of Seckel Syndrome Other forms of Seckel syndrome include SCKL2 (606744), caused by mutation in the RBBP8 gene (604124) on chromosome 18q11; SCKL4 (613676), caused by mutation in the CENPJ gene (609279) on chromosome 13q12; SCKL5 (613823), caused by mutation in the CEP152 gene (613529) on chromosome 15q21; SCKL6 (614728), caused by mutation in the CEP63 gene (614724) on chromosome 3q22; SCKL7 (614851), caused by mutation in the NIN gene (608684) on chromosome 14q22; SCKL8 (615807), caused by mutation in the DNA2 gene (601810) on chromosome 10q21; SCKL9 (616777), caused by mutation in the TRAIP gene (605958) on chromosome 3p21; SCKL10 (617253), caused by mutation in the NSMCE2 gene (617246) on chromosome 8q24; and SCKL11 (620767), caused by mutation in the CEP295 gene (617728) on chromosome 11q21. The report of a Seckel syndrome locus on chromosome 14q, designated SCKL3, by Kilinc et al. (2003) was found to be in error; see History section. [from OMIM]

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).
Clitoral hypertrophy
MedGen UID:
57848
Concept ID:
C0156394
Finding
Hypertrophy of the clitoris.
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.
Pes planus
MedGen UID:
42034
Concept ID:
C0016202
Anatomical Abnormality
A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced.
Dislocated radial head
MedGen UID:
488814
Concept ID:
C0265563
Congenital Abnormality
A dislocation of the head of the radius from its socket in the elbow joint.
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.
Talipes
MedGen UID:
220976
Concept ID:
C1301937
Congenital Abnormality
A deformity of foot and ankle that has different subtypes that are talipes equinovarus, talipes equinovalgus, talipes calcaneovarus and talipes calcaneovalgus.
Sandal gap
MedGen UID:
374376
Concept ID:
C1840069
Finding
A widely spaced gap between the first toe (the great toe) and the second toe.
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).
Hypoplasia of proximal radius
MedGen UID:
395274
Concept ID:
C1859477
Anatomical Abnormality
Proximal radial shortening owing to a congenital defect of development.
Hypoplasia of proximal fibula
MedGen UID:
347892
Concept ID:
C1859478
Finding
Underdevelopment or shortening of the end of the fibula (calf bone) nearest the knee.
Abnormal finger flexion crease
MedGen UID:
347157
Concept ID:
C1859481
Anatomical Abnormality
Anomalous flexion crease (i.e., a transverse line that crosses the skin of a finger).
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.
Proportionate short stature
MedGen UID:
163901
Concept ID:
C0878660
Finding
A kind of short stature in which different regions of the body are shortened to a comparable extent.
Postnatal growth retardation
MedGen UID:
395343
Concept ID:
C1859778
Finding
Slow or limited growth after birth.
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.
Abnormal pinna morphology
MedGen UID:
167800
Concept ID:
C0857379
Congenital Abnormality
An abnormality of the pinna, which is also referred to as the auricle or 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.
Macrogyria
MedGen UID:
120579
Concept ID:
C0266483
Congenital Abnormality
Pachygyria is a malformation of cortical development with abnormally wide gyri with sulci 1,5-3 cm apart and abnormally thick cortex measuring more than 5 mm (radiological definition). See also neuropathological definitions for 2-, 3-, and 4-layered lissencephaly.
Hyperactivity
MedGen UID:
98406
Concept ID:
C0424295
Finding
Hyperactivity is a condition characterized by constant and unusually high levels of activity, even in situations where it is deemed inappropriate.
Cerebellar vermis hypoplasia
MedGen UID:
333548
Concept ID:
C1840379
Finding
Underdevelopment of the vermis of cerebellum.
Large basal ganglia
MedGen UID:
395272
Concept ID:
C1859470
Finding
Increased size of the basal ganglia.
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.
Pancytopenia
MedGen UID:
18281
Concept ID:
C0030312
Disease or Syndrome
An abnormal reduction in numbers of all blood cell types (red blood cells, white blood cells, and platelets).
Hip dislocation
MedGen UID:
42455
Concept ID:
C0019554
Injury or Poisoning
Displacement of the femur from its normal location in the hip joint.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Elbow flexion contracture
MedGen UID:
98367
Concept ID:
C0409338
Acquired Abnormality
An elbow contracture that limits the ability of the elbow joint to be extended (straightened), meaning that the elbow is fixed in an flexed (bent) position.
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.
11 pairs of ribs
MedGen UID:
326950
Concept ID:
C1839731
Finding
Presence of only 11 pairs of ribs.
Ivory epiphyses
MedGen UID:
347330
Concept ID:
C1856911
Finding
Sclerosis of the epiphyses, leading to an increased degree of radiopacity (white or ivory appearance) in X-rays.
Small anterior fontanelle
MedGen UID:
347886
Concept ID:
C1859455
Finding
Abnormally decreased size of the anterior fontanelle with respect to age-dependent norms.
Cone-shaped epiphyses of the phalanges of the hand
MedGen UID:
347156
Concept ID:
C1859480
Finding
A cone-shaped appearance of the epiphyses of the fingers of the hand, producing a 'ball-in-a-socket' appearance. The related entity 'angel-shaped' epiphysis refers to a pronounced cone-shaped epiphysis in combination with a pseudoepiphysis at the distal end of a phalanx.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Blepharophimosis
MedGen UID:
2670
Concept ID:
C0005744
Anatomical Abnormality
A fixed reduction in the vertical distance between the upper and lower eyelids with short palpebral fissures.
Enamel hypoplasia
MedGen UID:
3730
Concept ID:
C0011351
Disease or Syndrome
Developmental hypoplasia of the dental enamel.
Dental malocclusion
MedGen UID:
9869
Concept ID:
C0024636
Anatomical Abnormality
Dental malocclusion refers to an abnormality of the occlusion, or alignment, of the teeth and the way the upper and lower teeth fit together, resulting in overcrowding of teeth or in abnormal bite patterns.
Dental crowding
MedGen UID:
11850
Concept ID:
C0040433
Finding
Changes in alignment of teeth in the dental arch
Convex nasal ridge
MedGen UID:
66809
Concept ID:
C0240538
Finding
Nasal ridge curving anteriorly to an imaginary line that connects the nasal root and tip. The nose appears often also prominent, and the columella low.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.
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.
Facial asymmetry
MedGen UID:
266298
Concept ID:
C1306710
Finding
An abnormal difference between the left and right sides of the face.
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.
Selective tooth agenesis
MedGen UID:
370882
Concept ID:
C1970308
Congenital Abnormality
Agenesis specifically affecting one of the classes incisor, premolar, or molar.
Cleft palate
MedGen UID:
756015
Concept ID:
C2981150
Congenital Abnormality
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.
Abnormally large globe
MedGen UID:
344595
Concept ID:
C1855852
Finding
Diffusely large eye (with megalocornea) without glaucoma.

Professional guidelines

PubMed

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

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Naseri N, Deepa B, Mathew AP, Oksman K, Girandon L
Biomacromolecules 2016 Nov 14;17(11):3714-3723. Epub 2016 Oct 25 doi: 10.1021/acs.biomac.6b01243. PMID: 27726351
Rauch A
Best Pract Res Clin Endocrinol Metab 2011 Feb;25(1):125-30. doi: 10.1016/j.beem.2010.10.015. PMID: 21396579

Diagnosis

Tabib A, Richmond CM, McGaughran J
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Am J Med Genet A 2020 Sep;182(9):2110-2116. Epub 2020 Jul 11 doi: 10.1002/ajmg.a.61754. PMID: 32652690Free PMC Article
Akkurt MO, Pakay K, Akkurt I, Temur M, Korkmazer E
J Matern Fetal Neonatal Med 2019 Jun;32(11):1905-1908. Epub 2017 Dec 28 doi: 10.1080/14767058.2017.1419467. PMID: 29284336
Alkuraya FS
Curr Opin Endocrinol Diabetes Obes 2015 Feb;22(1):55-64. doi: 10.1097/MED.0000000000000121. PMID: 25490023
Ramieri V, Tarani L, Costantino F, Basile E, Liberati N, Rinna C, Cascone P, Colloridi F
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Therapy

Scalet D, Balestra D, Rohban S, Bovolenta M, Perrone D, Bernardi F, Campaner S, Pinotti M
Biochim Biophys Acta Mol Basis Dis 2017 Jan;1863(1):15-20. Epub 2016 Sep 14 doi: 10.1016/j.bbadis.2016.09.011. PMID: 27639833
Stiff T, Casar Tena T, O'Driscoll M, Jeggo PA, Philipp M
Hum Mol Genet 2016 Apr 15;25(8):1574-87. Epub 2016 Feb 11 doi: 10.1093/hmg/ddw034. PMID: 26908596Free PMC Article
Darrigo LG Jr, Rodrigues MC, Pieroni F, Stracieri AB, Moraes DA, Grecco CE, Dias JB, Sobral AC, Simões BP
Pediatr Transplant 2014 May;18(3):E93-5. Epub 2014 Feb 1 doi: 10.1111/petr.12230. PMID: 24483323
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

Prognosis

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Scalet D, Balestra D, Rohban S, Bovolenta M, Perrone D, Bernardi F, Campaner S, Pinotti M
Biochim Biophys Acta Mol Basis Dis 2017 Jan;1863(1):15-20. Epub 2016 Sep 14 doi: 10.1016/j.bbadis.2016.09.011. PMID: 27639833
Ramieri V, Tarani L, Costantino F, Basile E, Liberati N, Rinna C, Cascone P, Colloridi F
J Craniofac Surg 2011 Nov;22(6):2124-8. doi: 10.1097/SCS.0b013e3182323cdf. PMID: 22067867

Clinical prediction guides

Scalet D, Balestra D, Rohban S, Bovolenta M, Perrone D, Bernardi F, Campaner S, Pinotti M
Biochim Biophys Acta Mol Basis Dis 2017 Jan;1863(1):15-20. Epub 2016 Sep 14 doi: 10.1016/j.bbadis.2016.09.011. PMID: 27639833
Murray JE, van der Burg M, IJspeert H, Carroll P, Wu Q, Ochi T, Leitch A, Miller ES, Kysela B, Jawad A, Bottani A, Brancati F, Cappa M, Cormier-Daire V, Deshpande C, Faqeih EA, Graham GE, Ranza E, Blundell TL, Jackson AP, Stewart GS, Bicknell LS
Am J Hum Genet 2015 Mar 5;96(3):412-24. Epub 2015 Feb 26 doi: 10.1016/j.ajhg.2015.01.013. PMID: 25728776Free PMC Article
Fitzgerald B, O'Driscoll M, Chong K, Keating S, Shannon P
Brain Dev 2012 Mar;34(3):238-43. Epub 2011 Jun 12 doi: 10.1016/j.braindev.2011.05.007. PMID: 21669506
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

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