Maple Syrup Urine Disease, Type 2 (DBT)

Maple syrup urine disease (MSUD), type 2 is an autosomal recessive disease caused by pathogenic variants in the gene DBT. Symptoms associated with this disorder begin in early infancy and are characterized by urine that has a maple syrup odor, poor feeding, vomiting, lethargy, seizures, hypertonicity, mental retardation, and developmental delay. If left untreated, this disease can lead to severe seizures, coma, central respiratory failure, and death. Life expectancy is normal for patients properly managed with a lifelong diet.

For information about carrier frequency and residual risk, please see the residual risk table.

This gene is included on the following panel(s):

Congenital Nongoitrous Hypothryoidism 4 (TSHB)

Congenital nongoitrous hypothryoidism 4 is an autosomal recessive disorder caused by pathogenic variants in the gene TSHB. The onset of this disorder is at birth and causes defective growth and development in newborns, and can lead to mental and growth retardation in infants if left untreated. Additional phenotypes may include a depressed nasal bridge, muscular hypotonia, macroglossia, umbilical hernia, and omphalocele. The life expectancy for this disorder is normal if treated.

For information about carrier frequency and residual risk, please see the residual risk table.

This gene is included on the following panel(s):

Xeroderma Pigmentosum, Group A (XPA)

Xeroderma pigmentosum (XP), group A is an autosomal recessive disorder caused by pathogenic variants in the gene XPA. This disorder is characterized by increased sensitivity to sunlight due to defects in DNA repair. Individuals present with skin lesions and freckling generally in sun-exposed areas as well as dry skin and changes in skin coloring. Individuals may also experience ocular symptoms, specifically eye irritation, corneal clouding, and impaired vision, as well as neurological symptoms, including hearing loss, poor coordination, difficulty walking, difficulty swallowing, and seizures. Individuals with this disorder have a significantly increased risk of developing skin cancer. No clear genotype-phenotype correlation has been established.

For information about carrier frequency and residual risk, please see the residual risk table.

This gene is included on the following panel(s):

Xeroderma Pigmentosum, Group C (XPC)

Xeroderma pigmentosum, group C (XP-C) is an autosomal recessive disorder caused by pathogenic variants in the gene XPC. This disorder is characterized by increased sensitivity to sunlight due to defects in DNA repair. Individuals present with skin lesions and freckling generally in sun-exposed areas as well as dry skin and changes in skin coloring. Individuals may also experience ocular symptoms, specifically eye irritation, corneal clouding, and impaired vision. Unlike other types of XP, individuals with XP group C typically do not have neurological symptoms. Individuals with this disorder have a significantly increased risk of developing skin cancer. No clear genotype-phenotype correlation has been established.

For information about carrier frequency and residual risk, please see the residual risk table.

This gene is included on the following panel(s):

Xeroderma Pigmentosum, Group G (ERCC5)

Xeroderma pigmentosum complementation group G (XP-G) is an autosomal recessive disorder caused by pathogenic variants in the gene ERCC5. XP group G is characterized by increased sensitivity to sunlight and defects in DNA repair. Individuals present with skin lesions and freckling generally in sun-exposed areas as well as dry skin and changes in skin coloring. Individuals may also experience ocular symptoms, specifically eye irritation, corneal clouding, and impaired vision. Some individuals with this disorder have neurological symptoms, such as developmental delay, ataxia, and spasticity. Individuals with this disorder have a significantly increased risk of developing skin cancer. Rarely, individuals may also exhibit symptoms such as short stature and pigmentary retinopathy. Pathogenic variants in ERCC5 can also result in a disorder called cerebrooculofacioskeletal syndrome 3 (COFS3) that impacts growth and development in utero. COFS3 is characterized by arthrogryposis, microcephaly, severe developmental delay, congenital cataracts, photophobia, and intellectual disability. No clear genotype-phenotype correlation has been established.

For information about carrier frequency and residual risk, please see the residual risk table.

This gene is included on the following panel(s):

Werner Syndrome (WRN)

Werner syndrome is an autosomal recessive disorder caused by pathogenic variants in the gene WRN. Werner syndrome is characterized by rapid appearance of features associated with normal aging. Symptoms of Werner syndrome typically become apparent around puberty. Teenagers do not experience a growth spurt and as a result are typically short. In their 20s, individuals with this disorder begin to develop symptoms of aging including gray hair, hair loss, hoarse voice, and a prematurely aged face. Individuals may also develop cataracts, diabetes, diminished fertility, atherosclerosis, osteoporosis, and cancer. Life expectancy is typically reduced to the 50s. No clear genotype-phenotype correlation has been established.

For information about carrier frequency and residual risk, please see the residual risk table.

This gene is included on the following panel(s):

Wiskott-Aldrich Syndrome, X-linked (WAS)

Pathogenic variants in the gene WAS cause Wiskott-Aldrich syndrome, which is inherited in an X-linked manner. Wiskott-Aldrich syndrome typically presents during infancy. Common clinical manifestations include thrombocytopenia, eczema, recurrent bacterial and viral infections, the risk of autoimmune disorders, and lymphoma. Although severe life-threatening infections, bleeding, autoimmune diseases, and malignancies have been commonly reported, life expectancy is not significantly affected with careful management of symptoms and infections.

For information about carrier frequency and residual risk, please see the residual risk table.

This gene is included on the following panel(s):

Wolcott-Rallison Syndrome (EIF2AK3)

Wolcott-Rallison Syndrome is a rare autosomal recessive disorder caused by pathogenic variants in the gene EIF2AK3. This disorder is typically characterized by neonatal or early-infancy insulin-dependent diabetes. Later, epiphyseal dysplasia, osteoporosis, and growth delays occur. Hepatic and renal dysfunction, intellectual disability, and cardiovascular abnormalities have been observed as well. Life expectancy may be reduced due to renal insufficiency, sequelae of poorly controlled diabetes, and multiorgan failure. No clear genotype-phenotype correlation has been established.

For information about carrier frequency and residual risk, please see the residual risk table.

This gene is included on the following panel(s):

Woodhouse-Sakati Syndrome (DCAF17)

Woodhouse-Sakati syndrome is an autosomal recessive disorder caused by pathogenic variants in the gene DCAF17. The onset of this disorder typically is in childhood or adolescence. This disorder primarily affects the endocrine system and nervous system. Affected individuals have hypogonadism and therefore do not develop secondary sexual characteristics such as breast growth in females and voice deepening in males. Females do not have functional ovaries and instead may have streak gonads as well as a small or absent uterus. Males produce little to no sperm. Both males and females with this condition are infertile. By adulthood, individuals typically develop diabetes, hypothyroidism, alopecia totalis, and postlingual sensorineural hearing loss. Almost half of affected individuals exhibit neurological symptoms such as dystonia, dysarthria, muscle contractions, and mild to severe intellectual disability. Some individuals have abnormal deposits of iron in their brain. This condition shows variable expressivity. The life expectancy and prevalence of this condition is unknown. No clear genotype-phenotype correlation has been established.

For information about carrier frequency and residual risk, please see the residual risk table.

This gene is included on the following panel(s):

Xeroderma Pigmentosum (POLH)

Xeroderma pigmentosum (POLH-related) is an autosomal recessive disorder caused by pathogenic variants in the gene POLH. This type of xeroderma pigmentosum is characterized by increased sensitivity to sunlight and defects in DNA repair. Individuals present with skin lesions and freckling generally in sun-exposed areas as well as dry skin and changes in skin coloring. Individuals may also experience ocular symptoms, specifically eye irritation, corneal clouding, and impaired vision, as well as neurological symptoms, including hearing loss, poor coordination, movement problems, difficulty swallowing, and seizures. Individuals with this disorder have a significantly increased risk of developing skin cancer. No clear genotype-phenotype correlation has been established.

For information about carrier frequency and residual risk, please see the residual risk table.

This gene is included on the following panel(s):