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Seckel Syndrome

Seckel syndrome (SS) is a hereditary autosomal recessive disease. It is extremely rare and typically causes dwarfism, mental retardation, intrauterine growth retardation and microcephaly. This disorder affects both males and females equally.


Presentation

Seckel syndrome has various forms, hence it shows a heterogeneous presentation [1]. Inherited in an autosomal recessive pattern, SS occurs through a mutation of one of the several genes, such as the retinoblastoma binding protein 8 (RBBP8) and centromere protein J (CENPJ) genes. It is recognized as part of a wider spectrum of autosomally recessive microcephalies [2]. SS has no preponderance for either sex and is not restricted to, or more common in, any particular geographical areas. Its incidence rate is estimated to be less than one in 1 million births.

The main features involve intrauterine growth restriction, microcephaly, continued growth impairment after birth leading to dwarfism, and skeletal abnormalities. A myriad of other characteristics has been described.

In addition to a reduced head circumference, patients have typical dysmorphic facial features which include narrow jaws and have been described to have a 'bird head' appearance. Cleft palate and high arched palate have been reported [3] [4]. Dental abnormalities such as poor enamel production, smaller and fewer teeth, and dental crowding, are common [5] [6]. The range of skeletal abnormalities, in addition to short stature, is broad and may include clinodactyly, bone dislocations (affecting the head of the femur), anomalies of limb, and spinal deformities such as kyphosis.

Mental retardation is usually recorded and may be mild to severe. In infancy and early childhood, affected individuals are slow in attaining developmental milestones.

Further systemic pathology has been associated with the syndrome, such as gastrointestinal, cardiovascular and ocular symptoms. There are also several central nervous system manifestations, for example, malformation of certain brain structures such as the cerebral cortex. A significant proportion of patients, as many as 15%, suffer from anemia, pancytopenia, leukemia or other forms of hematopathology [7]. They are prone to kidney and upper respiratory tract infections.

Short Stature
  • Seckel syndrome is an autosomal recessive condition with severe short stature and facial and neurological anomalies. Intracranial haemorrhage, due to rupture of a cerebral aneurysm, is a very rare complication of this syndrome.[ncbi.nlm.nih.gov]
  • One child had classical Seckel syndrome, a sib pair had the features of the syndrome with less severe short stature, and in two children the diagnosis was not confirmed.[ncbi.nlm.nih.gov]
  • The Seckel syndrome or "bird-headed" dwarfism associates a severe short stature, mental deficiency and various malformations with characteristic facial appearance. It has been described in these children a moderate or severe marrow hypoplasia.[ncbi.nlm.nih.gov]
  • Seckel syndrome is a rare autosomal recessive disease, genetically heterogeneous, characterized by short stature, prenatal microcephaly, intellectual disability, dysmorphic features, chromosomal instability, and hematological disorders.[ncbi.nlm.nih.gov]
  • Seckel syndrome is a very rare form of primordial dwarfism characterized by antenatal and postnatal growth delay, proportionate extreme short stature, a prominent beak-like nose, hypoplasia of the malar area, small chin, microcephaly, deformed ears lacking[ncbi.nlm.nih.gov]
Proportionate Short Stature
  • A homozygous nonsense mutation was identified in CEP63 in a consanguineous family of Pakistani descent with three members with primary microcephaly and proportionate short stature, clinically consistent with mild Seckel syndrome.[dnatesting.uchicago.edu]
  • .; and Krantz, I. (2011) "Proportionate short stature syndromes." Gorlin's Syndromes of the Head and Neck. Oxford, England: Oxford University Press:440-80.[rarediseases.about.com]
  • .; and Krantz, I. (2011) "Proportionate short stature syndromes." Gorlin's Syndromes of the Head and Neck . Oxford, England: Oxford University Press:440-80.[verywellhealth.com]
  • Characteristics of Seckel syndrome include severe proportionally short stature with severe microcephaly (mean postnatal growth retardation is -7SD with a range from -5 to -13 SD; mean OFC is -9SD with a range from -4 to -14SD), a ‘bird like’ profile include[dnatesting.uchicago.edu]
  • short stature 0003508 Seizures Seizure 0001250 Selective tooth agenesis 0001592 Single transverse palmar crease 0000954 Sloping forehead Inclined forehead Receding forehead [ more ] 0000340 Small anterior fontanelle 0000237 Small for gestational age[rarediseases.info.nih.gov]
Dysmorphic Face
  • face (bird-like), and mild to severe intellectual disability.[orpha.net]
  • A dysmorphic face with a receding chin and a relatively big nose could also render mask ventilation difficult. [11] Dental malocclusion, receding chin, high palatal arch could be the warning signs for the possibility of difficult intubation. [11] Although[joacp.org]
Single Transverse Palmar Crease
  • transverse palmar crease 0000954 Sloping forehead Inclined forehead Receding forehead [ more ] 0000340 Small anterior fontanelle 0000237 Small for gestational age Birth weight less than 10th percentile Low birth weight [ more ] 0001518 Strabismus Cross-eyed[rarediseases.info.nih.gov]
Delayed Growth and Development
  • Common features include a cleft in the lip or palate, abnormal facial features, limb or skeletal abnormalities, intellectual disability and delayed growth and development.[centogene.com]
High Pitched Voice
  • She also displayed high-pitched voice. The age of menarche was 15 years. She had regular menstrual cycles.[termedia.pl]
  • pitched voice 0001620 Percent of people who have these symptoms is not available through HPO 11 pairs of ribs 0000878 Abnormal finger flexion creases 0006143 Abnormality of the pinna Abnormally shaped ears Auricular malformation Deformed ears Malformed[rarediseases.info.nih.gov]
Heart Murmur
  • murmur Heart murmurs 0030148 High palate Elevated palate Increased palatal height [ more ] 0000218 Hip dislocation Dislocated hips Dislocation of hip [ more ] 0002827 Hyperactivity More active than typical 0000752 Hypoplasia of dental enamel Underdeveloped[rarediseases.info.nih.gov]
Selective Tooth Agenesis
  • tooth agenesis 0001592 Single transverse palmar crease 0000954 Sloping forehead Inclined forehead Receding forehead [ more ] 0000340 Small anterior fontanelle 0000237 Small for gestational age Birth weight less than 10th percentile Low birth weight [[rarediseases.info.nih.gov]
Alopecia
  • Affected individuals displayed telangiectases, alopecia, and other malignancies such as nonmelanoma skin cancer, and less commonly breast cancer and cervical cancer.[preventiongenetics.com]
  • 標題 トップオーサー 頁数 序文 黒木 良和 1 第II編 各論[2] 1 ichthyosis 金 慶彰 5 2 ichthyosis-cheek-eyebrow syndrome 金 慶彰 7 3 ichthyosis-coloboma-heart defect-deafness-mental retardation 金 慶彰 8 4 IFAP syndrome(ichthyosis follicularis, alopecia, and photophobia syndrome) 金 慶彰[nippon-rinsho.co.jp]
  • […] glomerulonephritis, type 3 Holoacardius Holoacardius acephalus Holoacardius acormus Holoacardius amorphus Holt-Oram syndrome Homologous chimera Hyperhidrosis, premature cavities and premolar aplasia Hyperthermia-induced defect Hypogonadism, diabetes mellitus, alopecia[icd9data.com]
  • […] with mental retardation syndrome type 2 PIGO Hyperphosphatasia with mental retardation syndrome type 3 PGAP2 Hyperphosphatasia with mental retardation syndrome type 4 PGAP3 Hyperphosphatasia with mental retardation syndrome type 5 PIGW Hypogonadism, alopecia[centogene.com]
  • […] virus Neonatal HSV infection - See Neonatal herpes Neonatal human immunodeficiency virus - See Congenital human immunodeficiency virus Neonatal hypothyroidism Neonatal ichthyosis-sclerosing cholangitis syndrome - See Ichthyosis, leukocyte vacuoles, alopecia[rarediseases.info.nih.gov]
Cafe-Au-Lait Spots
  • […] dental arches [ more ] 0000689 Dislocated radial head 0003083 Elbow flexion contracture Contractures of elbows Elbow contracture Elbow contractures [ more ] 0002987 Facial asymmetry Asymmetry of face Crooked face Unsymmetrical face [ more ] 0000324 Few cafe-au-lait[rarediseases.info.nih.gov]
Receding Hairline
  • We report on a 3-year-old boy with prenatal onset of proportionate dwarfism, postnatal severe microcephaly, high forehead with receded hairline, sparse scalp hair, beaked nose, mild retrognathia and hypotonia diagnosed at birth as Seckel syndrome.[ncbi.nlm.nih.gov]
Papule
  • We describe a 5-year-old girl with classic Seckel syndrome who presented with moderately severe atopic dermatitis and diffuse hypopigmented macules and papules.[ncbi.nlm.nih.gov]
Skeletal Dysplasia
  • Based on the clinical and radiological features showing evidence of skeletal dysplasia, the diagnosis was revised to Majewski osteodysplastic primordial dwarfism type II (MOPD II) syndrome.[ncbi.nlm.nih.gov]
  • The genes on this panel are included in the 3-M Syndrome / Primordial Dwarfism Panel, the Comprehensive Short Stature Syndrome Panel and the Comprehensive Growth Disorders / Skeletal Dysplasias and Disorders Panel.[blueprintgenetics.com]
  • The possible etiologic features for primary short stature could be due to skeletal dysplasias, chromosomal abnormalities, inborn errors of metabolism, intra-uterine growth retardation and miscellaneous syndromes including Russel-Silver Rubenstein Taybi[jisppd.com]
  • dysplasia, 3-M type 古庄 知己 649 333 skeletal dysplasia, Boomerang dysplasia 古庄 知己 651 334 skeletal dysplasia, de la Chapelle type 古庄 知己 653 335 skeletal dysplasia, Fuhrmann type 岡本 伸彦 655 336 skeletal dysplasia, Schneckenbecken type 岡本 伸彦 657 337 skeletal[nippon-rinsho.co.jp]
  • Seckel syndrome panel ATR, RBBP8, CENPJ, CEP152, CEP63, ATRIP Skeletal dysplasia ciliopathy panel DYNC2H1, EVC, EVC2, IFT43, IFT80,... Skeletal dysplasia extended panel ALPL, ARSE, COL10A1, COL11A1, COL11A2,...[centogene.com]
Beaked Nose
  • This syndrome is characterized by a proportionate dwarfism of prenatal onset, a severe microcephaly with a "bird-headed" like appearance (beaked nose, receding forehead, prominent eyes, and micrognathia), and mental retardation.[ncbi.nlm.nih.gov]
  • General appearance of the patient was characterized by small forehead, posteriorly slanted ears, slightly beaked nose, midfacial hypoplasia very stunted stature with microcephaly. He had borderline mental retardation with normal motor development.[ncbi.nlm.nih.gov]
  • Seckel syndrome is a rare entity characterized by marked growth retardation, microcephaly, facies characterized by receding forehead and chin, large beaked nose, and severe retardation, usually thought to be inherited as an autosomal recessive condition[ncbi.nlm.nih.gov]
  • We report on a 3-year-old boy with prenatal onset of proportionate dwarfism, postnatal severe microcephaly, high forehead with receded hairline, sparse scalp hair, beaked nose, mild retrognathia and hypotonia diagnosed at birth as Seckel syndrome.[ncbi.nlm.nih.gov]
  • Percentile for 21 weeks' gestation), a beaked nose, and increased nuchal fold thickness measurement (  95th percentile), low-set and prominent ears.[ncbi.nlm.nih.gov]
Narrow Face
  • Other characteristic facial features include abnormally large eyes, micrognathia, retrognathia, a narrow face, and low-set ears. Affected children may exhibit mental retardation.[accessanesthesiology.mhmedical.com]
  • Other features of SCKL include microcephaly (small head) with intellectual disability, unique facial features such as large eyes, narrow face, “beak-like” protrusion of the nose, and receding lower jaw. There are often skeletal bone abnormalities.[secure.ssa.gov]
  • Get Update Overview Seckel syndrome is a genetic disorder characterized by growth retardation, microcephaly with mental retardation, and unique facial features such as large eyes, beak-like nose, narrow face, and receding lower jaw.[diseaseinfosearch.org]
  • The findings include: very small at birth (average birth weight is 1,540 g or about 3.3 pounds) extremely small proportionate stature (dwarfism) very small head (microcephaly) "beak-like" protrusion of the nose narrow face malformed ears unusually small[walkingwithgiants.org]
  • General appearance of the patient was characterized by a small, narrow face and forehead, slightly beaked nose, midfacial hypoplasia, very stunted stature with microcephaly (Figure 1). She also displayed high-pitched voice.[termedia.pl]
Hyperactivity
  • Most children with Seckel syndrome are "friendly and pleasant" but "often hyperkinetic (hyperactive) and easily distracted." This disease is genetic. It is inherited in an autosomal recessive manner.[medicinenet.com]
  • Growth failure Growth retardation Poor growth Retarded growth [ more ] 0001510 Heart murmur Heart murmurs 0030148 High palate Elevated palate Increased palatal height [ more ] 0000218 Hip dislocation Dislocated hips Dislocation of hip [ more ] 0002827 Hyperactivity[rarediseases.info.nih.gov]

Workup

There are several tools used in the workup of SS, including clinical assessment.

A diagnosis may be made prenatally, via ultrasound in the second trimester, by identifying intrauterine growth restriction (IUGR). A series of ultrasound scans can be conducted, making the technique more effective in detecting abnormalities in the bone structure and facial features [8].

On presentation during childhood, the examination is carried out by noting anthropometric measurements, including head circumference, height, and weight. Evaluation of the morphology of the pelvic bones and femur is also useful.

Other methods include:

  • Imaging of the skeletal system: This is to assess delayed bone maturation and deformities [9].
  • Magnetic resonance imaging (MRI) scan of the brain: Malformations may be visualized.
  • Analysis of neurocognitive and motor abilities, as well as neurological examination.
  • Electroencephalogram (EEG): Monitoring for seizures.
Delayed Bone Age
  • Other characteristics include microcephaly, mild to moderate mental retardation, characteristic narrow bird-like face with a beak-like nose, large eyes, micrognathia, delayed bone age, hip dysplasia, and elbow dislocation (Faivre et al. 2002).[preventiongenetics.com]
Ischemic Changes
  • Imaging studies revealed multiple completed cerebral infarcts, global ischemic changes, and vascular anatomy consistent with moyamoya syndrome.[ncbi.nlm.nih.gov]

Treatment

  • Serum levels of immunoreactive IGF-1, bioactive IGF-1, and IGF-binding protein 3 were all within normal to high range before GH treatment and increased after GH treatment. Fasting plasma ghrelin remained severely reduced.[ncbi.nlm.nih.gov]
  • Treatment included extractions, periodontal therapy, retention of premolars with sealants, and overdentures with resilient soft liners. A limited review of Seckel syndrome literature is included.[ncbi.nlm.nih.gov]
  • Considering the patient's previous quality of life and the high risks of either endovascular or surgical treatment, all invasive treatments were withheld at the parents' request and only palliative care was offered.[ncbi.nlm.nih.gov]
  • We found that, compared with controls, there is greater chromosomal instability, particularly at fragile sites, in SCKL1-affected patient cells after treatment with aphidicolin, an inhibitor of DNA polymerase alpha and other polymerases.[ncbi.nlm.nih.gov]
  • The patient died 1 year later of complications related to treatment of a rapidly progressing intracranial aneurysm. This report documents the first case associating moyamoya and Seckel syndromes.[ncbi.nlm.nih.gov]

Prognosis

  • The main features of the syndrome, technical problems encountered during surgery and the prognosis of this condition are discussed.[ncbi.nlm.nih.gov]
  • Forms and Documents Test Details Clinical Utility: Molecular confirmation of a clinical diagnosis Establish the type of microcephaly and cause in order to provide information regarding prognosis, management and recurrence risk.[genedx.com]
  • This integrated partnership has contributed to the improvement of procedures aimed at the diagnosis, prognosis and intervention of individuals with genetic syndromes and communication disorders as early as possible.[scielo.br]

Etiology

  • Look at other dictionaries: Virchow-Seckel syndrome — (also known as bird headed dwarfism, Harper s syndrome or Seckel dwarfism) is a syndrome of unknown etiology, characterized by intrauterine growth retardation and postnatal dwarfism with a small head[medicine.academic.ru]
  • The possible etiologic features for primary short stature could be due to skeletal dysplasias, chromosomal abnormalities, inborn errors of metabolism, intra-uterine growth retardation and miscellaneous syndromes including Russel-Silver Rubenstein Taybi[jisppd.com]

Epidemiology

  • Multicentre study, aiming to determine morphological and epidemiological parameters and identify new symptoms in French patients with SCKL or MOPDII.[clinicaltrials.gov]
  • Genetic epidemiology and nonsyndromic structural birth defects: from candidate genes to epigenetics. JAMA pediatrics, 168(4), 371-377. Parker SE, Mai CT, Canfield MA, Rickard R, Wang Y, Meyer RE, Correa A (2010).[centogene.com]
Sex distribution
Age distribution

Prevention

  • Malignant hypertension may play an important role in the aetiology of the aneurysm and early detection is essential in order to prevent organ damage. we report a new case of Seckel syndrome associated with malignant hypertension and cerebral haemorrhage[ncbi.nlm.nih.gov]
  • These phenotypes are prevented using p38 inhibitors, with replicative capacity restored to the normal range.[ncbi.nlm.nih.gov]
  • Replicative stress, a source of endogenous DNA damage, is prevented primarily by the ATR kinase. We have developed a mouse model of Seckel syndrome characterized by a severe deficiency in ATR.[ncbi.nlm.nih.gov]
  • The material is waterproof and insures good defence against corrosion preventing any water and oxygen from coming in contact with chassis. Added mineral fillers assure safety for human health and environment.[xwave.one]
  • Prevention of secondary complications: Physical therapy to prevent joint contractures; aggressive dental care to minimize dental caries; home safety assessment to prevent falls.[ncbi.nlm.nih.gov]

References

Article

  1. Faivre L, Cormier-Daire V. Orphanet encyclopedia. Seckel Syndrome. https://www.orpha.net/data/patho/GB/uk-Seckel(05).pdf. Published July 2001. Updated April 2005. Accessed May 17, 2017.
  2. HarshaVardhan BG, Muthu MS, Saraswathi K, Koteeswaran D. Bird-Headed Dwarf of Seckel. J Indian Soc Pedod Prev Dent. 2007;25(5):8-9.
  3. Seymen F, Tuna B, Kayserili H. Seckel syndrome: Report of a case. J Clin Pediatr Dent. 2002;26(3):305-309.
  4. Kjaer I, Hansen N, Becktor KB, Birkebaek N, Balslev T. Craniofacial morphology, dentition and skeletal maturity in four siblings with Seckel syndrome. Cleft Palate Craniofac J. 2001;38(6):645-651.
  5. De Coster PJ, VerbeecK RM, Holthaus V, Martens LC, Vral A. Seckel syndrome associated with oligodontia, microdontia, enamel hypoplasia, delayed eruption, and dentin dysmineralization: A new variant? J Oral Pathol Med. 2006;35(10):639-641.
  6. Elalaoui SC, Mariam T, Ilham R, Yassamine D, Abdelaziz S. A recurrent mutation in Moroccan patients with Dyggve-Melchior-Clausen syndrome: Report of a new case and review. Indian J Hum Genet. 2011;17(2):97-99.
  7. Chanan-Khan A, Holkova B, Perle MA, et al. T-cell clonality and myelodysplasia without chromosomal fragility in a patient with features of Seckel syndrome. Haematologica 2003;88(5):ECR14.
  8. De Elejalde MM, Elejalde BR. Visualisation of the fetal face by ultrasound. J Craniofac Genet Dev Biol. 1984;4(4):251-257.
  9. Poznanski AK, Iannaccone G, Pasquino AM, Boscherini B. Radiological findings in the hand in Seckel syndrome (bird-headed dwarfism). Pediatr Radiol. 1983;13(1):19–24.

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Last updated: 2019-06-28 12:11