Cornelia de Lange syndrome 2

Cornelia de Lange Syndrome 2 (CDLS2)

Cornelia de Lange Syndrome 2, also known as CDLS2, is a rare genetic disorder caused by mutations in the SMC1A gene. This gene encodes a subunit of the cohesin complex, which plays a crucial role in DNA repair and cell cycle regulation.

Key Features:

• Genetic Cause: CDLS2 is caused by heterozygous mutation in the SMC1A gene on chromosome Xp11.
• Developmental and Epileptic Encephalopathy: Individuals with CDLS2 may experience developmental delays, intellectual disability, and seizures (epilepsy).
• Sex-Specific: This condition primarily affects females, as males have an extra copy of the X chromosome, which can compensate for the mutated gene.

Other Relevant Information:

• Cornelia de Lange Syndrome 2 is a rare genetic disorder that affects growth and development.
• The symptoms of CDLS2 vary widely among affected individuals and range from mild to severe.
• Individuals with CDLS2 may experience characteristic facial features, such as thin, downturned lips and low-set ears.

References:

• [1] Evidence suggests that mutations in the SMC1A gene cause Cornelia de Lange Syndrome-2 (CDLS2).
• [3] Severe (classic) CdLS is characterized by distinctive facial features, growth restriction, hypertrichosis, and upper-limb reduction defects.
• [6] An X-linked inherited form of Cornelia De Lange syndrome caused by mutations in the SMC1A gene mapped to chromosome Xp11.22.

Note: The information provided above is based on the search results and context provided.

Distinctive Facial Features

Cornelia de Lange syndrome is characterized by a set of distinctive facial features, which can vary in severity among individuals. Some common signs include:

• Thin, downturned lips
• Low-set ears
• Arched, well-defined eyebrows that grow together across the base of the nose [2][9]

These facial features are often present at birth and may become more pronounced as the individual grows older.

Other Common Symptoms

In addition to distinctive facial features, Cornelia de Lange syndrome can also cause a range of other symptoms, including:

• Slowing of body growth
• Cognitive issues
• Diaphragmatic hernias
• Vision and hearing problems
• Excessive body hair (hirsutism)
• Heart defects
• Seizures
• Dental issues [3][4]

It's worth noting that the severity of these symptoms can vary widely among individuals, and not everyone with Cornelia de Lange syndrome will exhibit all of these characteristics.

Diagnostic Tests for Cornelia de Lange Syndrome (CdLS)

Cornelia de Lange syndrome (CdLS) is a rare genetic disorder that can be diagnosed through various tests. Here are some of the diagnostic tests used to confirm CdLS:

• Genetic Testing: Genetic testing is the most effective way to diagnose CdLS. It involves sequencing and deletion/duplication analysis of the genes NIPBL, SMC3, RAD21, SMC1A, and HDAC8 [4][8]. Gene panels should at least include the causal genes for a definitive diagnosis [7].
• Molecular Genetic Diagnosis: Molecular genetic diagnosis can be performed using sequencing and deletion/duplication analysis of the above-mentioned genes. This test is usually recommended when there are suspicions of CdLS based on clinical features [4][8].
• Auditory Brain Stem Response Testing and Otoacoustic Emissions Testing: These tests may be included in the diagnostic workup to assess hearing function, as some individuals with CdLS may have hearing impairments [1].

Other Diagnostic Considerations

In addition to these specific tests, a comprehensive diagnostic evaluation for CdLS should also include:

• Echocardiography and Renal Sonography: Routine echocardiography and renal sonography are indicated in every diagnosed infant and child, given that 25% of individuals with CdLS have cardiac or renal abnormalities [6].
• Intellectual Disability Assessment: Intellectual disability is a common feature of CdLS. Assessing the level of intellectual disability can help confirm the diagnosis.

References

[1] MA Deardorff · 2020 · Cited by 148 — Diagnosis/testing. [4] Jul 21, 2023 — Molecular genetic diagnosis can be performed using sequencing and deletion/duplication analysis of NIPBL, SMC3, RAD21, SMC1A, and HDAC8. [6] by AD Kline · 2018 · Cited by 378 — Routine echocardiography and renal sonography are indicated in every diagnosed infant and child... [7] The diagnosis is confirmed by genetic testing for up to 70% of patients presenting a classical phenotype. Gene panels should at least include the causal genes... [8] Jul 21, 2023 — Molecular genetic diagnosis can be performed using sequencing and deletion/duplication analysis of the genes NIPBL, SMC3, RAD21, SMC1A, and...

Treatment Options for Cornelia de Lange Syndrome

Cornelia de Lange syndrome (CdLS) can be managed with a combination of medication and lifestyle changes to alleviate symptoms and improve quality of life.

• Proton Pump Inhibitors (PPIs): PPIs are often prescribed to manage gastroesophageal reflux disease (GERD), which is common in individuals with CdLS [2]. These medications can help reduce stomach acid and prevent symptoms such as heartburn and regurgitation.
• Feeding Difficulties: Feeding difficulties are a hallmark of CdLS, particularly in infants and young children. Oral feeding is preferred if possible, but in some cases, tube feeding may be necessary to ensure adequate nutrition [3].
• Surgery: In some cases, surgery may be required to manage symptoms such as GERD or joint contractures [4]. However, this should only be considered on a case-by-case basis and under the guidance of a qualified healthcare professional.
• Early Intervention: Early intervention is crucial for individuals with CdLS, particularly in terms of psychomotor delay. Computer programs that emphasize visual memory can be beneficial in improving cognitive function [5].
• Prenatal Genetic Testing: Prenatal genetic testing can identify gene mutations associated with CdLS, allowing for early diagnosis and management [6].

It's essential to note that treatment plans are tailored to the individual child, taking into account their unique needs and circumstances. A multidisciplinary team of healthcare professionals should be involved in developing a comprehensive care plan.

References: [2] Kline AD (2018) - Clinical practice with proton pump inhibitors in children and adults with Cornelia de Lange syndrome. [3] Kline AD (2018) - Feeding difficulties in individuals with Cornelia de Lange syndrome. [4] Treatment for GERD varies by age but can include medication to reduce stomach acid or make the stomach empty faster. Your doctor may also recommend surgery in some cases [7]. [5] Early intervention for psychomotor delay is also indicated. Computer programs that emphasize visual memory are more beneficial than standard programs [5]. [6] Prenatal genetic testing can identify gene mutations for the condition [6]. [8] Cornelia de Lange syndrome (CdLS) encompasses a spectrum of findings from mild to severe, with severe (classic) CdLS being characterized by distinctive facial features [8].

Differential Diagnoses for Cornelia de Lange Syndrome

Cornelia de Lange syndrome (CdLS) can be challenging to diagnose due to its variable presentation and overlap with other genetic conditions. Here are some differential diagnoses that should be considered:

• Fryns syndrome: This rare condition is characterized by a distinctive facial appearance, growth restriction, and intellectual disability. It shares similarities with CdLS in terms of its severe phenotype.
• Dup(3q) syndrome: This condition involves a duplication of the long arm of chromosome 3 and can present with similar features to CdLS, including growth restriction and intellectual disability.
• Fetal Alcohol Syndrome (FAS): While FAS is caused by prenatal alcohol exposure, it can share some physical characteristics with CdLS, such as facial dysmorphia and growth restriction. However, FAS typically lacks the distinctive facial features of CdLS.

It's essential to consider these differential diagnoses when evaluating patients for CdLS, especially in cases where the phenotype is atypical or mild. A comprehensive diagnostic workup, including genetic testing and clinical evaluation, can help differentiate between these conditions.

References:

• [1] Jul 21, 2023 — Differential Diagnoses · Dup(3q) syndrome · Fetal Alcohol Syndrome · Fryns syndrome.
• [5] Jun 2, 2022 — Differential Diagnoses. Coffin-Siris syndrome. Dermatologic Manifestations of Hirsutism · Fetal Alcohol Syndrome.
• [6] by AD Kline · 2018 · Cited by 378 — Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, and growth restriction.