Norman-Roberts syndrome

Norman-Roberts Syndrome: A Rare Neurodevelopmental Disorder

Norman-Roberts syndrome, also known as Microlissencephaly type A or Lissencephaly syndrome Norman-Roberts type, is a rare and severe neurodevelopmental disorder characterized by the association of lissencephaly type I with craniofacial anomalies [1][2].

Clinical Characteristics

The clinical features of Norman-Roberts syndrome include:

• Microcephaly (small head size)
• Bitemporal hollowing
• Low sloping forehead
• Slightly prominent occiput
• Widely set eyes
• Broad and prominent nasal bridge
• Lymphedema (swelling of the lymph nodes)
• Hypotonia (low muscle tone)
• Cerebellar hypoplasia (underdeveloped cerebellum)
• Classic lissencephaly (smooth brain appearance)
• Generalized seizures [3][4]

Associated Features

Patients with Norman-Roberts syndrome may also experience:

• Myopia (nearsightedness)
• Nystagmus (involuntary eye movements)
• Congenital lymphedema
• Hypotonia

These features are often present at birth or develop in early childhood, and can vary in severity from one individual to another [5].

Diagnosis

The diagnosis of Norman-Roberts syndrome is typically made through a combination of clinical evaluation, imaging studies (such as MRI), and genetic testing. Early recognition and diagnosis are crucial for providing appropriate medical care and support for affected individuals and their families [6][7].

References:

[1] Context 2 [2] Context 7 [3] Context 5 [4] Context 4 [5] Context 8 [6] Context 9 [7] Context 6

Signs and Symptoms of Norman-Roberts Syndrome

Norman-Roberts syndrome, also known as lissencephaly syndrome, is a rare genetic disorder characterized by severe intellectual disability, seizures, and physical abnormalities. The signs and symptoms of this condition can vary widely from person to person, even among members of the same family.

Common Signs and Symptoms:

• Microcephaly: Small head size
• Low sloping forehead: A distinctive feature of Norman-Roberts syndrome
• Broad and prominent nasal bridge: A characteristic facial feature
• Widely set eyes: Eyes that are farther apart than usual
• Seizures: Severe seizures, including infantile spasms, can occur
• Muscle spasms: Muscle stiffness or rigidity
• Developmental delays: Delayed development of motor skills and cognitive abilities
• Growth retardation: Slow growth before and after birth

Additional Abnormalities:

• Feeding difficulties: Trouble feeding due to muscle weakness or other complications
• Impaired motor abilities: Weakness or paralysis in the arms and legs
• Profound intellectual disability: Severe cognitive impairment, often requiring special care and support

Variability of Symptoms:

It's essential to note that the symptoms of Norman-Roberts syndrome can vary significantly from person to person. Some individuals may experience mild symptoms, while others may have more severe manifestations.

References:

• [1] - Microcephaly is a characteristic feature of Norman-Roberts syndrome (Source 2)
• [2] - Low sloping forehead and broad nasal bridge are distinctive facial features (Source 3)
• [3] - Widely set eyes, seizures, muscle spasms, and developmental delays are common symptoms (Source 4)
• [4] - Feeding difficulties, impaired motor abilities, and profound intellectual disability can also occur (Source 5)

Diagnostic Tests for Norman-Roberts Syndrome

Norman-Roberts syndrome, also known as Lissencephaly syndrome, Norman-Roberts type, is a rare genetic disorder characterized by the association of lissencephaly type I with craniofacial anomalies. Diagnostic tests play a crucial role in confirming the diagnosis and identifying the underlying mutation responsible for the condition.

Imaging Studies

• Ultrasound: Ultrasound can detect microcephaly, which is a major sign of Norman-Roberts syndrome (Source: [6])
• MRI: Magnetic Resonance Imaging (MRI) is essential for diagnosing Norman-Roberts syndrome, particularly for the closed-lipped type and to define the associated anomalies (Source: [4])

DNA Studies

• Chromosomal Analysis: DNA studies, such as chromosomal analysis, are used to find the mutation responsible for Norman-Roberts syndrome (Source: [7])
• Specific Gene Mutational Analysis: Providers use specific gene mutational analysis to confirm the diagnosis and identify the underlying mutation (Source: [7])

Other Diagnostic Criteria

• Growth Restriction: Growth restriction is one of the clinical diagnostic criteria for Norman-Roberts syndrome (Source: [9])
• Symmetric Mesomelic Shortening of Limbs: Symmetric mesomelic shortening of the limbs and characteristic facies with microcephaly are also part of the clinical diagnostic criteria (Source: [9])

It's essential to note that a comprehensive evaluation requires a combination of imaging studies, DNA analysis, and clinical diagnostic criteria. A team of healthcare professionals, including geneticists, radiologists, and pediatricians, should work together to confirm the diagnosis and develop an appropriate treatment plan.

References: [1] - Not available in context [2] - Not available in context [3] - Not available in context [4] - Although ultrasound can make the diagnosis, a more complete evaluation requires MRI, particularly for the closed-lipped type and to define the associated anomalies. [5] - Norman-Roberts type is characterized by the association of lissencephaly type I with craniofacial anomalies (severe microcephaly, a low sloping forehead) [6] - The major sign was the ultrasound detection of microcephaly at the 22nd and 23rd week of gestation. Fetal Magnetic Nuclear Resonance, the ... [7] - To confirm the diagnosis, providers use DNA studies, such as chromosomal analysis and specific gene mutational analysis, to find the mutation responsible for ... [8] - Not available in context [9] - Clinical diagnostic criteria include growth restriction, symmetric mesomelic shortening of the limbs, and characteristic facies with microcephaly. Upper limbs ...

Treatment Options for Norman-Roberts Syndrome

Norman-Roberts syndrome, also known as lissencephaly syndrome, Norman-Roberts type, is a rare genetic disorder characterized by the association of lissencephaly type I with craniofacial anomalies. While there is no cure for this condition, various treatment options can help manage its symptoms.

• Medications to control seizures: People living with Norman-Roberts syndrome may experience seizures, which can be managed through medications. Physical, occupational, and speech therapy may also be beneficial in some cases [3].
• Targeted treatment of specific symptoms: Healthcare providers focus on treating the specific symptoms that each child with Norman-Roberts syndrome experiences. This approach allows for personalized care and can help improve quality of life [8].

It's essential to note that there is no main treatment or cure for lissencephaly, including Norman-Roberts syndrome. However, by targeting specific symptoms and providing supportive care, individuals with this condition can lead fulfilling lives.

Available Genetic Tests

For families affected by Norman-Roberts syndrome, genetic testing may be an option to confirm the diagnosis. The RELN gene mutation is associated with this condition, and various genetic tests are available from US labs and around the world [7].

References: [3] - May 4, 2023 — Physical, occupational, and speech therapy could help in some cases. People living with the condition might need medications to control seizures ... [7] - Clinical resource with information about Norman-Roberts syndrome and its clinical features, RELN, available genetic tests from US and labs around the world ... [8] - There's no cure or main treatment for lissencephaly. Instead, healthcare providers target treatment toward the specific symptoms that each child with ...

Differential Diagnosis of Norman-Roberts Syndrome

Norman-Roberts syndrome, also known as LIS2, is a rare genetic disorder that shares similarities with other lissencephaly syndromes. The differential diagnosis for Norman-Roberts syndrome includes:

• Isolated Lissencephaly: A condition characterized by a smooth brain surface without any cortical folding.
• Miller-Dieker Syndrome: A severe form of lissencephaly that is often associated with deletion of the chromosome 17.
• Microlissencephaly (MLIS): A rare congenital brain disorder that combines severe microcephaly (small head) with lissencephaly.

These conditions share similar clinical manifestations, including growth restriction, symmetric mesomelic shortening of the limbs, and characteristic facies with microcephaly. However, autopsy findings may differ substantially between these syndromes, leading to a differential diagnosis that requires careful consideration of various factors [3][8].

Key Features

• Growth restriction
• Symmetric mesomelic shortening of the limbs
• Characteristic facies with microcephaly
• Seizures, profound intellectual disability, feeding difficulties, growth retardation, and impaired motor abilities may also be present [5]

It is essential to note that Norman-Roberts syndrome has a distinct genetic cause, which involves a mutation of the RELN gene. This genetic difference can help differentiate it from other lissencephaly syndromes [3].

References

[1] Context result 3: A mutation of the RELN gene causes Norman-Roberts syndrome, which includes lissencephaly. [2] Context result 8: LIS2: Norman-Roberts syndrome, similar to type I lissencephaly or Miller-Dieker syndrome, but without deletion of the chromosome 17. [3] Context result 9: However, autopsy findings differed substantially, leading us to conclude that the clinical manifestations of Norman-Roberts syndrome are not unique to it. [5] Context result 5: Additional abnormalities may include seizures, profound intellectual disability, feeding difficulties, growth retardation, and impaired motor abilities. If an ... [8] Context result 8: LIS2: Norman-Roberts syndrome, similar to type I lissencephaly or Miller-Dieker syndrome, but without deletion of the chromosome 17.