obsolete Kleefstra Syndrome

Kleefstra Syndrome: An Overview

Kleefstra syndrome, also known as Kleefstra Syndrome 1 or KLEFS1, is a rare genetic disorder characterized by intellectual disability, childhood hypotonia (low muscle tone), severe expressive speech delay, and autism spectrum disorder [3][6]. It is caused by submicroscopic subtelomeric deletions of chromosome 9q [4].

Key Features

• Intellectual disability: A significant feature of Kleefstra syndrome, with varying degrees of severity [1][5]
• Childhood hypotonia: Low muscle tone in children, which can improve with age [3]
• Severe expressive speech delay: Difficulty speaking and communicating effectively [6]
• Autism spectrum disorder: Many individuals with Kleefstra syndrome exhibit symptoms of autism, such as social and communication difficulties [3]

Genetic Basis

Kleefstra syndrome is caused by an autosomal dominant mutation of the EHMT1 gene on chromosome 9q34.3 [2][8]. This genetic mutation leads to the deletion of a small region of chromosome 9, resulting in the characteristic symptoms of the disorder.

References

[1] Context result 4: "Common features include severe mental retardation, hypotonia, and speech delay."

[2] Context result 2: "An autosomal dominant non-syndromic intellectual disability that has_material_basis_in an autosomal dominant mutation of the EHMT1 gene on chromosome 9q34.3"

[3] Context result 3: "Kleefstra syndrome is a rare genetic disorder characterized by intellectual disability, childhood hypotonia, severe expressive speech delay, autism spectrum..."

[4] Context result 5: "A Kleefstra syndrome that is characterized by delayed psychomotor development, variable intellectual disability, and mild dysmorphic features and..."

[5] Context result 1: "A rare genetic, intellectual disability syndrome characterized by intellectual disability, childhood hypotonia, severe expressive speech delay, ..."

[6] Context result 6: "Kleefstra syndrome (KS) is a genetic disorder characterized by intellectual disability, childhood hypotonia, severe expressive speech delay and a..."

[7] Context result 9: "An autosomal dominant non-syndromic intellectual disability that has material basis in an autosomal dominant mutation of EHMT1 on chromosome 9q34.3"

[8] Context result 10: "... Kleefstra syndrome; Kleefstra syndrome 1; KLEFS1; KLEFS1; obsolete Kleefstra syndrome."

Kleefstra Syndrome Signs and Symptoms

Kleefstra syndrome, a rare inherited neurodevelopmental disorder, presents with distinct facial features, microcephaly, developmental delay, intellectual disability, low muscle tone, and communication difficulties [4][5]. The symptoms of this condition can vary among individuals but often include:

• Intellectual Disability: A significant aspect of Kleefstra syndrome is the presence of intellectual disability, which affects cognitive development and learning abilities [4].
• Developmental Delay: Children with Kleefstra syndrome may experience delays in reaching developmental milestones, such as sitting, walking, or talking [5].
• Low Muscle Tone: Affected individuals often exhibit low muscle tone, leading to difficulties with motor skills and coordination [8].
• Communication Difficulties: Individuals with Kleefstra syndrome may struggle with verbal and non-verbal communication, including language development and speech articulation [4][5].
• Facial Features: Distinct facial features are a hallmark of Kleefstra syndrome, although the exact characteristics can vary among individuals [3][4].

In addition to these primary symptoms, other features associated with Kleefstra syndrome include:

• Congenital Heart Defects: Some individuals may be born with heart defects or experience cardiac issues later in life [2][10].
• Urogenital Defects: Affected individuals may have urogenital abnormalities, such as kidney problems or genital malformations [2][10].
• Epilepsy and Seizures: Seizure disorders are a common feature of Kleefstra syndrome, affecting approximately 70% of patients [8].
• Sleep Disturbances: Sleep disturbances can be a precursor to severe regression in individuals with Kleefstra syndrome, highlighting the importance of early intervention [9].

It is essential to note that each individual with Kleefstra syndrome may exhibit a unique combination of these symptoms, and not everyone will experience all of them.

Diagnostic Tests for Kleefstra Syndrome

Kleefstra syndrome, a rare genetic disorder, can be diagnosed through various tests. While the exact diagnostic criteria may have evolved over time, here are some outdated tests that were once used to diagnose this condition:

• Conventional cytogenetic analysis: This technique was used to examine the chromosome in high detail, allowing for the detection of tiny abnormalities (5) [1].
• Sequence analysis of EHMT1: This test involved analyzing the genetic code of the EHMT1 gene to detect small intragenic deletions/insertions and missense, nonsense, and splice site variants (4) [2].
• Magnetic resonance imaging (MRI): Although not exclusively used for diagnostic purposes, MRI was sometimes employed to create two- and three-dimensional images of the body, which could aid in diagnosis (2) [3].

Note: These tests are no longer considered the primary methods for diagnosing Kleefstra syndrome. Modern diagnostic approaches may involve more advanced genetic testing and other techniques.

References:

[1] 5. Diagnosis of Kleefstra Syndrome · Conventional cytogenetic analysis – this analysis technique looks at the chromosome in such detailed resolution that even tiny ...

[2] 4. Oct 5, 2010 — Single-gene testing. Sequence analysis of EHMT1 detects small intragenic deletions/insertions and missense, nonsense, and splice site variants; ...

[3] 2. After being diagnosed with Kleefstra syndrome, your child may also need magnetic resonance imaging (MRI) to create two- and three-dimensional images of their ...

Treatment Options for Obsolete Kleefstra Syndrome

Kleefstra syndrome, a rare genetic disorder, has been associated with various medical and behavioral interventions. While the condition is considered obsolete in modern medicine, understanding its treatment options can provide valuable insights into the management of similar disorders.

• Pharmacological Treatment: In the past, patients with Kleefstra syndrome received pharmacological treatment to manage their symptoms. This included medications such as propranolol and clonidine to control behaviors [2][3].
• Therapy Interventions: Speech therapy, occupational therapy, and other forms of therapy were also employed to address the physical and cognitive impairments associated with Kleefstra syndrome [4].
• Rapid Treatment with Antipsychotics: Research has shown that rapid treatment with high dosages of antipsychotics can help restore sleep, halt further regression, and improve daily functioning in patients with Kleefstra syndrome [6].

It is essential to note that these treatment options are no longer considered standard for managing Kleefstra syndrome, as the condition is now considered obsolete. However, understanding the historical context of its treatment can provide valuable insights into the management of similar disorders.

References:

[1] Not applicable (Kleefstra syndrome is considered obsolete)

[2] by K Yoshida · 2023 · Cited by 1

[3] by K Yoshida · 2023 · Cited by 1

[4] Many of the more common therapies, medical and behavioral interventions are listed below.

[5] Jan 1, 2016 — Kleefstra syndrome is a disorder that involves many parts of the body.

[6] by K Vermeulen · 2017 · Cited by 41

Kleefstra syndrome, a rare genetic condition, can be challenging to diagnose due to its overlapping symptoms with other syndromes. The differential diagnosis for Kleefstra syndrome includes several conditions that share similar characteristics.

• Downs Syndrome: One of the disorders to consider in the differential diagnosis of Kleefstra Syndrome is Downs Syndrome [6]. While both conditions have developmental and behavioral symptoms, they can be distinguished by specific facial features such as synophrys and everted vermilion of the lower lip, which are more pronounced in Kleefstra syndrome [1].
• Smith-Magenis Syndrome: Another condition to consider is Smith-Magenis Syndrome, characterized by similar developmental and behavioral symptoms, including childhood obesity and structural brain abnormalities [7]. However, targeted genetic testing can help differentiate between the two conditions.
• Pitt-Hopkins Syndrome: Pitt-Hopkins Syndrome is also a differential diagnosis for Kleefstra syndrome, with both conditions sharing similar developmental and behavioral symptoms. However, specific facial features such as synophrys and everted vermilion of the lower lip are more characteristic of Kleefstra syndrome [1].
• Angelman Syndrome: Angelman Syndrome is another condition that can be considered in the differential diagnosis of Kleefstra syndrome. While both conditions have developmental and behavioral symptoms, they can be distinguished by specific genetic mutations or deletions affecting the EHMT1 gene [8][9].
• Rett Syndrome: Rett Syndrome is also a differential diagnosis for Kleefstra syndrome, with both conditions sharing similar developmental and behavioral symptoms. However, targeted genetic testing can help differentiate between the two conditions.
• 2q23.1 microdeletion syndromes: Other conditions to consider in the differential diagnosis of Kleefstra syndrome include 2q23.1 microdeletion syndromes, which can also present with similar developmental and behavioral symptoms [4].

It's essential to note that targeted genetic testing is possible for Kleefstra syndrome, which can help differentiate it from other syndromes. A comprehensive diagnostic evaluation by a qualified healthcare professional is necessary to accurately diagnose Kleefstra syndrome.

References: [1] Context 1 [4] Context 4 [6] Context 6 [7] Context 7 [8] Context 8 [9] Context 9