Seckel syndrome, or microcephalic

primordial dwarfism Primordial dwarfism (PD) is a form of dwarfism that results in a smaller body size in all stages of life beginning from before birth. More specifically, primordial dwarfism is a diagnostic category including specific types of profoundly proportion ...

(also known as bird-headed dwarfism, Harper's syndrome, Virchow–Seckel dwarfism and bird-headed dwarf of Seckel) is an extremely rare

congenital A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can ...

nanosomic disorder. Inheritance is

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

. It is characterized by

intrauterine growth restriction Intrauterine growth restriction (IUGR), or fetal growth restriction, refers to poor growth of a fetus while in the womb during pregnancy. IUGR is defined by clinical features of malnutrition and evidence of reduced growth regardless of an infant's ...

and postnatal

dwarfism Dwarfism is a condition wherein an organism is exceptionally small, and mostly occurs in the animal kingdom. In humans, it is sometimes defined as an adult height of less than , regardless of sex; the average adult height among people with dw ...

with a

small head Microcephaly (from New Latin ''microcephalia'', from Ancient Greek μικρός ''mikrós'' "small" and κεφαλή ''kephalé'' "head") is a medical condition involving a smaller-than-normal head. Microcephaly may be present at birth or it ...

, narrow bird-like face with a beak-like nose, large eyes with down-slanting

palpebral fissure The palpebral fissure is the elliptic space between the medial and lateral canthi of the two open eyelids. In simple terms, it is the opening between the eyelids. In adult humans, this measures about 10 mm vertically and 30 mm horizontally. Var ...

s, receding

mandible In anatomy, the mandible, lower jaw or jawbone is the largest, strongest and lowest bone in the human facial skeleton. It forms the lower jaw and holds the lower tooth, teeth in place. The mandible sits beneath the maxilla. It is the only movabl ...

and

intellectual disability Intellectual disability (ID), also known as general learning disability in the United Kingdom and formerly mental retardation,Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010). is a generalized neurodevelopmental disorder characterized by signifi ...

. A mouse model has been developed. This mouse model is characterized by a severe deficiency of

ATR ATR may refer to: Medicine * Acute transfusion reaction * Ataxia telangiectasia and Rad3 related, a protein involved in DNA damage repair Science and mathematics * Advanced Test Reactor, nuclear research reactor at the Idaho National Laboratory, ...

protein. These mice have high levels of replicative stress and

DNA damage DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA da ...

. Adult Seckel mice display accelerated ageing. These findings are consistent with the

DNA damage theory of aging The DNA damage theory of aging proposes that aging is a consequence of unrepaired accumulation of naturally occurring DNA damage. Damage in this context is a DNA alteration that has an abnormal structure. Although both mitochondrial and nuclear ...

Symptoms and signs

Symptoms include: *

(more than half of the patients have an IQ below 50) *

microcephaly Microcephaly (from New Latin ''microcephalia'', from Ancient Greek μικρός ''mikrós'' "small" and κεφαλή ''kephalé'' "head") is a medical condition involving a smaller-than-normal head. Microcephaly may be present at birth or it ...

* sometimes

pancytopenia Pancytopenia is a medical condition in which there is significant reduction in the number of almost all blood cells (red blood cells, white blood cells, platelets, monocytes, lymphocytes, etc.). If only two parameters from the complete blood coun ...

(low blood counts) *

cryptorchidism Cryptorchidism, also known as undescended testis, is the failure of one or both testes to descend into the scrotum. The word is from Greek () 'hidden' and () 'testicle'. It is the most common birth defect of the male genital tract. About 3% of ...

in males * low birth weight * dislocations of pelvis and elbow * unusually large eyes * blindness or visual impairment * large, low-set ears * small chin due to receded lower jaw

Genetics

It is believed to be caused by defects of genes on

chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...

3 and 18. One form of Seckel syndrome can be caused by mutation in the gene encoding the ataxia telangiectasia and Rad3-related protein () which maps to chromosome 3q22.1-q24. This gene is central in the cell's DNA damage response and repair mechanism. Types include:

Diagnosis

Treatment

History

The syndrome was named after German-American physician Helmut Paul George Seckel (1900–1960). The synonym Harper's syndrome was named after Rita G. Harper.

References

External links

* {{Nucleus diseases Congenital disorders Growth disorders Syndromes affecting head size Syndromes affecting stature Syndromes with intellectual disability Rare syndromes