Tag Archives: inheritance

Muscular Dystrophy – Charcot Marie Tooth

© 2018, GENASSIST, Inc.

By Keith S. Wexler, MBA, CFO, Business Development Director GENASSIST, Inc.

Paul Wexler, M.D., F.A.C.O.G., Medical Director, GENASSIST, Inc.

Clinical Professor, Department of OB/GYN, University of Colorado Health Sciences Center

Clinical Professor, Division of Genetics/Dept. of Pediatrics, Univ. of Colorado/The Children’s Hospital

Background:  We are working with a family here in the United States and in Europe in an attempt to help identify the familial gene for Charcot-Marie-Tooth Disease (CMT) so that the daughters can attempt IVF with Preimplantation Genetic Diagnosis (PGD).

Analysis:  Charcot-Marie-Tooth Disease (CMT) is one of the most common hereditary motor and sensory neuropathies. The condition was named after Jean Martin Charcot and Pierre Marie in Paris and Howard Henry Tooth in Cambridge, England, who first described the condition in 1886.

The incidence of Charcot-Marie-Tooth is approximately 1 in 2500 in the United States although it varies regionally being 1 in 1214 in Norway and 1 in 6500 in the United Kingdom. 

At least 14 types of CMT disease have been described:

  • 7 inherited in an autosomal dominant manner
  • 3 in an autosomal recessive manner
  • 4 types that are inherited in a sex (X) linked recessive manner.

The most common mode of inheritance is autosomal dominant in which only one deleterious (disease causing) mutation can result in the disease affecting 1:2 (50%) of children, male or female inheriting the disease causing mutation from one affected parent. One of the common characteristics of an autosomal dominantly inherited condition is variable expression in which the severity of the presenting symptoms may vary considerably.

CMT Type 1:

  • Believed to be inherited in an autosomal dominant manner, sex (X) linked dominant inheritance and less commonly sporadic (de novo) mutations have also been reported. The various types of CMT have been divided into subtypes based on the known causative mutations and their chromosomal locations.

Autosomal Recessive Inheritance of Charcot-Marie-Tooth Disease requires the inheritance of one deleterious gene from each unaffected carrier parent. The disease is often earlier in onset and more severe. 25% (1 in 4) children will be affected, 25% (1 in 4) children will inherit only the normal unaffected allele and be unaffected and non-carrier and 50% (1 in 2) will inherit one deleterious gene from only one parent and be an unaffected carrier like each parent. Male and female children are equal risk.

Sex (X) Linked Recessive Inheritance is caused when an unaffected carrier mother passes a deleterious mutation on one X chromosome to a child. Affected males having only one X chromosome will pass the affected X to all female children who will be “unaffected” carriers or usually have milder disease. Male children from an affected father will receive their father’s Y chromosome and be unaffected. Carrier females will have a 50% (1 in 2) risk of passing their deleterious X chromosome to each male child. Female children have a 50% (1 in 2) risk of inheriting the deleterious X chromosome and be a carrier female like their mother.

Symptoms often include:

  • Weakness and sensory loss in arms and legs
  • Numbness in the feet
  • Depressed tendon reflexes
  • High foot arches or hammer toes
  • Ultimate muscle weakness and wasting
  • Decreased sensation in hands and feet
  • Increased tendency toward injury which may go unnoticed.

The diagnosis is often made clinically. However, multiple DNA gene panels are available including analyzing peripheral blood for 17 genes, 45 genes or 82 genes depending on the likely mode of inheritance including causative genes and several preliminary evidence genes.

Rarely the same disorder or a similar disorder (phenocopy) can result from a different cause and involve other genes.

Neonatology – Agenesis of the Corpus Callosum (ACC)

© 2018, GENASSIST, Inc.    

By Keith S. Wexler, MBA, CFO, Business Development Director, GENASSIST, Inc.

Paul Wexler, M.D., F.A.C.O.G., Medical Director, GENASSIST, Inc.

Clinical Professor, Department of OB/GYN, University of Colorado Health Sciences Center

Clinical Professor, Division of Genetics/Dept. of Pediatrics, Univ. of Colorado/The Children’s Hospital

Agenesis of the Corpus Callosum (ACC) is when the corpus callosum that connects both hemispheres of the brain in a fetus only partially develops or does not develop (agenesis) in pregnancy.

Agenesis of the Corpus Callosum Symptoms:

  • Low muscle tone
  • Vision and hearing difficulties
  • Variable developmental delay
  • Swallowing and feeding difficulties
  • Occasional seizures

Incidence: 1-7 per 1000 births

Agenesis of the Corpus Callosum can be inherited in an autosomal recessive manner, X linked dominant inheritance or be due to a new mutation in the fetus or can also be attributed to an infection or excessive alcohol consumption in pregnancy.

Autosomal recessive diseases are due to a child inheriting one deleterious gene from each parent. That couple’s recurrence risk for another child with Agenesis of the Corpus Callosum could approach 25% (1 in 4).

X linked dominant inheritance is due to the inheritance of one deleterious gene on one X chromosome from an affected parent, or can be due to a new mutation (de novo).

Several gene mutations have been implicated in the disorder:

  • Mutation in the SLC12A6 gene on the short arm of chromosome #15 (15q13-14)
  • ARX gene on the short arm of the X chromosome (Xp22.13)
  • SZT2 mutations on the short arm of chromosome #1 (1p34.2) and may be associated with seizures
  • DCC mutations on the long arm of chromosome #18 (18q21.3)

Several genetic companies are offering panels for mutational analysis for children with Agenesis of the Corpus Callosum.

Most Pediatric Neurologists are aware of this testing. However, not all cases will be diagnosed by these genetic tests.

 

Charcot Marie Tooth

© 2018, GENASSIST, Inc.

By Keith S. Wexler, MBA, CFO, Business Development Director GENASSIST, Inc.

Paul Wexler, M.D., F.A.C.O.G., Medical Director, GENASSIST, Inc.

Clinical Professor, Department of OB/GYN, University of Colorado Health Sciences Center

Clinical Professor, Division of Genetics/Dept. of Pediatrics, Univ. of Colorado/The Children’s Hospital

Background:  We are working with a family here in the United States and in Europe in an attempt to help identify the familial gene for Charcot-Marie-Tooth Disease (CMT) so that the daughters can attempt IVF with Preimplantation Genetic Diagnosis (PGD).

Analysis:  Charcot-Marie-Tooth Disease (CMT) is one of the most common hereditary motor and sensory neuropathies. The condition was named after Jean Martin Charcot and Pierre Marie in Paris and Howard Henry Tooth in Cambridge, England, who first described the condition in 1886.

The incidence of Charcot-Marie-Tooth is approximately 1 in 2500 in the United States although it varies regionally being 1 in 1214 in Norway and 1 in 6500 in the United Kingdom. 

At least 14 types of CMT disease have been described:

  • 7 inherited in an autosomal dominant manner
  • 3 in an autosomal recessive manner
  • 4 types that are inherited in a sex (X) linked recessive manner.

The most common mode of inheritance is autosomal dominant in which only one deleterious (disease causing) mutation can result in the disease affecting 1:2 (50%) of children, male or female inheriting the disease causing mutation from one affected parent. One of the common characteristics of an autosomal dominantly inherited condition is variable expression in which the severity of the presenting symptoms may vary considerably.

CMT Type 1:

  • Believed to be inherited in an autosomal dominant manner, sex (X) linked dominant inheritance and less commonly sporadic (de novo) mutations have also been reported. The various types of CMT have been divided into subtypes based on the known causative mutations and their chromosomal locations.

Autosomal Recessive Inheritance of Charcot-Marie-Tooth Disease requires the inheritance of one deleterious gene from each unaffected carrier parent. The disease is often earlier in onset and more severe. 25% (1 in 4) children will be affected, 25% (1 in 4) children will inherit only the normal unaffected allele and be unaffected and non-carrier and 50% (1 in 2) will inherit one deleterious gene from only one parent and be an unaffected carrier like each parent. Male and female children are equal risk.

Sex (X) Linked Recessive Inheritance is caused when an unaffected carrier mother passes a deleterious mutation on one X chromosome to a child. Affected males having only one X chromosome will pass the affected X to all female children who will be “unaffected” carriers or usually have milder disease. Male children from an affected father will receive their father’s Y chromosome and be unaffected. Carrier females will have a 50% (1 in 2) risk of passing their deleterious X chromosome to each male child. Female children have a 50% (1 in 2) risk of inheriting the deleterious X chromosome and be a carrier female like their mother.

Symptoms often include:

  • Weakness and sensory loss in arms and legs
  • Numbness in the feet
  • Depressed tendon reflexes
  • High foot arches or hammer toes
  • Ultimate muscle weakness and wasting
  • Decreased sensation in hands and feet
  • Increased tendency toward injury which may go unnoticed.

The diagnosis is often made clinically. However, multiple DNA gene panels are available including analyzing peripheral blood for 17 genes, 45 genes or 82 genes depending on the likely mode of inheritance including causative genes and several preliminary evidence genes.

Rarely the same disorder or a similar disorder (phenocopy) can result from a different cause and involve other genes.

Reproductive Medicine – Charcot Marie Tooth

© 2018, GENASSIST, Inc.

By Keith S. Wexler, MBA, CFO, Business Development Director GENASSIST, Inc.

Paul Wexler, M.D., F.A.C.O.G., Medical Director, GENASSIST, Inc.

Clinical Professor, Department of OB/GYN, University of Colorado Health Sciences Center

Clinical Professor, Division of Genetics/Dept. of Pediatrics, Univ. of Colorado/The Children’s Hospital

Background:  We are working with a family here in the United States and in Europe in an attempt to help identify the familial gene for Charcot-Marie-Tooth Disease (CMT) so that the daughters can attempt IVF with Preimplantation Genetic Diagnosis (PGD).

Analysis:  Charcot-Marie-Tooth Disease (CMT) is one of the most common hereditary motor and sensory neuropathies. The condition was named after Jean Martin Charcot and Pierre Marie in Paris and Howard Henry Tooth in Cambridge, England, who first described the condition in 1886.

The incidence of Charcot-Marie-Tooth is approximately 1 in 2500 in the United States although it varies regionally being 1 in 1214 in Norway and 1 in 6500 in the United Kingdom. 

At least 14 types of CMT disease have been described:

  • 7 inherited in an autosomal dominant manner
  • 3 in an autosomal recessive manner
  • 4 types that are inherited in a sex (X) linked recessive manner.

The most common mode of inheritance is autosomal dominant in which only one deleterious (disease causing) mutation can result in the disease affecting 1:2 (50%) of children, male or female inheriting the disease causing mutation from one affected parent.

One of the common characteristics of an autosomal dominantly inherited condition is variable expression in which the severity of the presenting symptoms may vary considerably.

CMT Type 1:

  •  Believed to be inherited in an autosomal dominant manner, sex (X) linked dominant inheritance and less commonly sporadic (de novo) mutations have also been reported. The various types of CMT have been divided into subtypes based on the known causative mutations and their chromosomal locations.

Autosomal Recessive Inheritance of Charcot-Marie-Tooth Disease requires the inheritance of one deleterious gene from each unaffected carrier parent. The disease is often earlier in onset and more severe. 25% (1 in 4) children will be affected, 25% (1 in 4) children will inherit only the normal unaffected allele and be unaffected and non-carrier and 50% (1 in 2) will inherit one deleterious gene from only one parent and be an unaffected carrier like each parent. Male and female children are equal risk.

Sex (X) Linked Recessive Inheritance is caused when an unaffected carrier mother passes a deleterious mutation on one X chromosome to a child. Affected males having only one X chromosome will pass the affected X to all female children who will be “unaffected” carriers or usually have milder disease. Male children from an affected father will receive their father’s Y chromosome and be unaffected. Carrier females will have a 50% (1 in 2) risk of passing their deleterious X chromosome to each male child. Female children have a 50% (1 in 2) risk of inheriting the deleterious X chromosome and be a carrier female like their mother.

Symptoms often include:

  • Weakness and sensory loss in arms and legs
  • Numbness in the feet
  • Depressed tendon reflexes
  • High foot arches or hammer toes
  • Ultimate muscle weakness and wasting
  • Decreased sensation in hands and feet
  • Increased tendency toward injury which may go unnoticed.

The diagnosis is often made clinically. However, multiple DNA gene panels are available including analyzing peripheral blood for 17 genes, 45 genes or 82 genes depending on the likely mode of inheritance including causative genes and several preliminary evidence genes.

Rarely the same disorder or a similar disorder (phenocopy) can result from a different cause and involve other genes. 

Contact GENASSIST™

Fill out my online form.