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 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

  Abstract Seckel syndrome is a heterogeneous, autosomal recessive disorder marked by prenatal proportionate short stature, severe microcephaly, intellectual disability, and characteristic facial features. [zora.uzh.ch]

  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]

• 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]

• Cyanotic Congenital Heart Disease

  Tricuspid atresia is a rare and life threatening cyanotic congenital heart diseases, with an incidence of 1% to 3%. [ncbi.nlm.nih.gov]

• 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]

  […] 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]

  […] 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]

• 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]

• 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]

• Hypopigmented Macule

  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 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]

  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. * The CPT codes provided are based on [blueprintgenetics.com]

• Short Forearm

  The mother of this girl was short, microcephalic, and had disproportionately short forearms and legs. In view of this, dominant inheritance of the disease was suggested. [ncbi.nlm.nih.gov]

• 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]

  Seck·el syn·drome ( sek'ĕl ), [MIM*210600] an autosomal recessive disorder characterized by low birth weight, dwarfism, microcephaly, large eyes, beaked nose, receding mandible, and moderate mental retardation. [medical-dictionary.thefreedictionary.com]

• 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]

  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]

  face malformed ears unusually small jaw (micrognathia) mental retardation, often severe (IQ less than 50) Other symptoms may include abnormally large eyes, high arched roof of the mouth (palate), tooth malformation, and other bone abnormalities. [natureblind.blogspot.com]

• Bird-like Facies

  Seckel syndrome is an autosomal recessive disorder characterized by severe intrauterine growth retardation, microcephalic bird-like facies, and a mental retardation. [go.gale.com]

• 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]

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

  It is associated with webbed toes, nondescended testicles, hypospadias, weak muscle tone, and delayed bone age.[4] The heights of individuals in Russell-Silver and Meier-Gorlin syndrome exceed when compared to other primordial dwarfism.[4] Seckel syndrome [go.gale.com]

  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]

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.