Seckel Syndrome - Causes, Symptoms, Diagnosis and Treatment

What Is Seckel Syndrome?

Seckel syndrome is a rare genetic syndrome that results in restricted growth, both prenatally and postnatally. Growth restriction in the intrauterine period (gestation or baby growth period) results in poor birth weight, and limited growth after birth results in dwarfism or short height. Studies about the clinical and genetic heterogeneity relationship have yet to be proven. Recent studies have shown chromosomal instability in the fragile sites where replication stress was described, and there is an interlinking between chromosomal instability and phenotypic findings.

Seckel Syndrome and Primordial Dwarfism:

It is a rare primordial dwarfism characterized by low birth weight babies with short height and a small head. Primordial dwarfism comprises rare genetic disorders that cause dwarfism (abnormally small build of people). Hence, they are also called small head big body syndrome. These babies may also have an intellectual disability with facial features like a sloping forehead, and the nose may be in a beak shape. Other features of this disease include a narrow face with large eyes, an atypical ear shape, and a small jaw, also known as micrognathia. Bodily features include hip dysplasia, characterized by unusual hip development with radial dislocation (forearm dislocation), along with a condition known as clinodactyly, in which there can be a curve in the little finger.

What Are the Other Names of Seckel Syndrome?

• Seckel type dwarfism.

• Nanocephalic dwarfism.

• Seckel type primordial dwarfism.

• SCKL.

• Microcephalic primordial dwarfism.

• Virchow-Seckel syndrome.

• Small head, big body syndrome.

• Bird-headed dwarfism.

• Harper syndrome.

• Seckel nanism.

What Are the Subdivisions of Seckel Syndrome?

Depending on the gene affected, Seckel syndrome is subdivided into ten types, namely,

• Seckel syndrome 1 or SCKL1.

• Seckel syndrome 2 or SCKL2.

• Seckel syndrome 3 or SCKL3.

• Seckel syndrome 4 or SCKL4.

• Seckel syndrome 5 or SCKL5.

• Seckel syndrome 6 or SCKL6.

• Seckel syndrome 7 or SCKL7.

• Seckel syndrome 8 or SCKL8.

• Seckel syndrome 9 or SCKL9.

• Seckel syndrome 10 or SCKL10.

What Is the Cause of Seckel Syndrome?

Seckel syndrome is a rare form of a genetic disorder. It exhibits an autosomal recessive pattern. It is caused due to mutations, which are changes occurring in the genes. In the case of recessive disorders, parents who have undergone consanguineous marriages share a higher chance of giving birth to a child who can either be a carrier or an affected individual of the disease than unrelated parents.

This recessive genetic disorder occurs when two non-working genes are inherited from each parent. If one working gene and one non-working gene are inherited, the person becomes a carrier. Carriers are usually asymptomatic. There is a 25 percent chance that a child will be affected by Seckel syndrome. The child is 50 percent likely to become a carrier when two parents are carriers. The chances for the child to become healthy by receiving only healthy genes from the carrier parents are 25 percent. Seckel syndrome is subdivided into ten types depending on the gene affected. The following are the subdivisions and the genes involved in each subdivision:

What Is the Incidence of Seckel Syndrome?

Ever since it was first diagnosed in 1960, there have been around 100 cases of Seckel syndrome. Hence, it is a rare genetic disorder. Since it is a rare disease, it occurs in only one in 10,000 people. Many such affected children are found to be born to consanguineous married parents, especially first siblings or cousins. Also, since it follows a recessive pattern, the baby shall receive one abnormal gene from each parent. If the other parent does not have a recessive gene, then the baby will be a carrier of the gene and will not show any symptoms of this disease.

How Is Seckel Syndrome Manifested?

Before birth, it causes reduced fetal growth, resulting in low birth weight. After birth, manifestations of Seckel syndrome include reduced growth and delayed bone maturation. The following are the symptoms seen in Seckel syndrome:

• Achondroplasia or short-limbed dwarfism.

• Low birth weight.

• Short stature.

• The nose shows a beak-like protrusion.

• The face appears narrow.

• Small-sized head or microcephaly.

• Micrognathia or small jaw.

• Ear malformation.

• Retardation of mental ability. Sometimes, the intelligence quotient (IQ) can be significantly less than 50.

• Abnormalities of the tooth.

• Blood disorders like pancytopenia (low number of blood cells), anemia (lack of healthy red blood cells or dysfunctional red blood cells), and acute myeloid leukemia (an aggressive type of cancer in the blood and bone marrow).

• Abnormal-shaped eyes or large eyes.

• High-arched palate.

• Cryptorchidism (an abnormal condition in which one or both testicles have not moved into the scrotum) or undescended testis (testicles not moved to the proper place in the scrotum).

• Unusually large clitoris.

• The presence of a simian crease is a solitary and deep line on the palm that forms during embryonic development.

What Are the Diagnostic Criteria for Seckel Syndrome?

• Prenatal onset of proportionate dwarfism.

• Presence of autosomal recessive inheritance.

• Retardation of mental growth.

• Severe microcephaly.

• Bird-headed appearance.

How Is Seckel Syndrome Diagnosed?

1. Family History: Genetic counselors examine a person's family history of the disease to determine the chances of acquiring this syndrome.

2. Brain Imaging: Microcephaly is an essential characteristic of Seckel syndrome, which imaging tests can identify. Two standard deviations of the mean value of age, gender, and ethnicity are determined for the child. If the occipitofrontal head circumference (maximum circumference of the head) present at birth is less than this value, the diagnosis of Seckel syndrome is confirmed.

3. Molecular Genetic Testing: Gene mutations can also be identified by performing molecular genetic tests, helping diagnose Seckel syndrome. In a couple with a child with Seckel syndrome, antenatal molecular diagnosis can help identify the condition in the fetus.

4. Fetal Ultrasound: Fetal growth retardation can be noted in the fetal ultrasound taken in the second trimester of pregnancy. However, this can help detect only high-risk cases, and this method cannot diagnose low-risk patients.

How Can We Treat Seckel Syndrome?

There is no specific cure for this condition, and symptomatic management is recommended. The bone and tooth abnormalities are fixed in early childhood to reduce functional difficulties. Medical management is done for blood disorders like anemia, pancytopenia, and acute myeloid leukemia. For mentally challenged children and their parents, counseling and social support are provided.

Conclusion:

Seckel syndrome is an inherited condition that poses physical and mental disabilities to the affected child. This leads to mental trauma to the family of that child. If you know you have a family history of the disease, consulting a doctor during pregnancy to detect antenatal deformities is vital.