obsolete Fryns syndrome

Fryns Syndrome: An Obsolete Condition

Fryns syndrome, as described in the past, was a rare multiple congenital anomaly syndrome characterized by several distinct features.

• Congenital Diaphragmatic Hernia: A condition where there is a hole in the diaphragm, allowing abdominal organs to move into the chest cavity.
• Pulmonary Hypoplasia: Underdeveloped lungs, which can lead to breathing difficulties and other respiratory problems.
• Distal Limb Hypoplasia: Underdevelopment of the fingers and toes (digits).
• Dysmorphic Facial Features: Abnormal facial features, such as a wide-set eyes, a wide and depressed nasal bridge with a broad nasal tip, long philtrum, low-set and anomalous ears, tented vermilion of the upper lip, wide mouth, and a small jaw.

According to some sources [3][4], Fryns syndrome was considered a lethal, autosomal recessive syndrome of multiple congenital anomalies. However, it's essential to note that this condition has been obsoleted from the Orphanet nomenclature of rare diseases [4].

The original diagnostic criteria for Fryns syndrome included abnormal facies; small thorax with widely spaced, hypoplastic nipples; distal limb and digital abnormalities; and other associated malformations [13]. However, these criteria have undergone modifications over time as more cases were reported and studied.

It's worth noting that the current understanding of Fryns syndrome has evolved, and it is no longer considered a distinct medical condition. Instead, similar cases are often classified under other syndromes or conditions, such as Lethal chondrodysplasia [4].

Fryns syndrome, also known as Fryns-Aftimos syndrome, is a rare genetic disorder that affects the development of multiple parts of the body. The signs and symptoms of this condition can vary widely among affected individuals.

Classical Findings

• Cloudy cornea
• Brain malformations
• Diaphragmatic defects (such as congenital diaphragmatic hernia)
• Distal limb deformities

These classical findings are often present in patients with Fryns syndrome, but the severity and manifestation of these symptoms can vary greatly from one individual to another.

Other Associated Features

• Early onset mildly reduced intellectual function
• Facial asymmetry
• Dystonic tremor of hands and neck
• Large head size
• Tall thin body habitus
• Long thin face
• Prominent nasal bridge
• High narrow palate
• Short distal phalanges of the fingers and toes

These features can be present in individuals with Fryns syndrome, but they may not necessarily be part of the classical findings. The presence of these symptoms can make diagnosis more challenging.

Mortality Risk

Fryns Syndrome is considered an autosomal recessive disorder that has a high mortality chance due to the serious symptoms associated with it. The most common symptom is CDH, which could result in the movement of organs located in the abdominal cavity, such as the liver, inside the thoracic cavity where the heart and lungs are located.

Differential Diagnosis

Symptoms of disorders like Congenital Diaphragmatic Hernia (CDH), Greig Cephalopolysyndactyly Syndrome (GCPS), and other genetic conditions may be similar to those of Fryns syndrome. A differential diagnosis is essential to accurately diagnose this condition.

References:

• [3] Fryns-Aftimos syndrome (MIM 606155) is a rare condition characterised by pachygyria, severe mental retardation, epilepsy and characteristic facial features.
• [10] Fryns syndrome is a condition that affects the development of many parts of the body. Signs and symptoms vary widely among affected individuals.
• [13] Fryns syndrome is characterized by diaphragmatic defects (diaphragmatic hernia, eventration, hypoplasia, or agenesis); characteristic facial appearance (coarse facies, wide-set eyes, a wide and depressed nasal bridge with a broad nasal tip, long philtrum, low-set and anomalous ears, tented vermilion of the upper lip, wide mouth, and a small jaw); short distal phalanges of the fingers and toes.
• [15] Fryns Syndrome is considered an autosomal recessive disorder that has a high mortality chance due to the serious symptoms associated with it.

Based on the provided context, it appears that diagnostic tests for Fryns syndrome have evolved over time.

Traditional Diagnostic Methods

In the past, chromosome analysis was a common method used to diagnose Fryns syndrome. This involved analyzing the chromosomes in peripheral lymphocytes (1). However, most routine cultured lymphocyte chromosome analyses would not demonstrate isochromosome 12p, leaving Fryns syndrome as the most likely diagnosis (3, 5).

Current Diagnostic Approaches

Today, molecular diagnosis of Intellectual Disability, including whole exome sequencing, may be used to diagnose Fryns syndrome (4). This approach involves analyzing the entire genome for genetic mutations that could be associated with the condition.

Other Diagnostic Considerations

It's worth noting that congenital diaphragmatic hernia can also present with other congenital anomalies, and Fryns syndrome may be the most common autosomal recessive syndrome associated with this condition (9). Additionally, understanding which providers on your diagnostic team have advanced medical training in different body systems or types of diseases can help you find the correct diagnosis sooner (10).

Incidence and Inheritance

Fryns syndrome is inherited in an autosomal recessive manner, meaning that each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier (11). The incidence of Fryns syndrome is estimated to be around 1/14,000 births (14).

Clinical Presentation

Fryns syndrome is characterized by diaphragmatic defects, characteristic facial appearance, short distal phalanges of the fingers and toes, and other congenital anomalies (15). The clinical diagnosis of Fryns syndrome can be established in a proband based on these characteristics.

References:

(1) Cytogenetic testing. Chorionic villus sampling (CVS) or amniocentesis for chromosome analysis (G-banded or Q-banded karyotype) are offered in many institutions. (3) Most routine cultured lymphocyte chromosome analyses will not demonstrate isochromosome 12p, leaving Fryns syndrome as the most likely diagnosis. Our case ... (4) Knowledge on rare diseases and orphan drugs · Search for a diagnostic test · Molecular diagnosis of Intellectual Disability (whole exome sequencing). (5) Most routine cultured lymphocyte chromosome analyses will not demonstrate isochromosome 12p, leaving Fryns syndrome as the most likely diagnosis. Our case ... (9) Congenital diaphragmatic hernia can also present with other congenital anomalies. Fryns syndrome (229850) may be the most common autosomal recessive syndrome ... (10) Providers on your diagnostic team have advanced medical training in different body systems or types of diseases. (11) Fryns syndrome is inherited in an autosomal recessive manner, meaning that each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. (14) Fryns Syndrome (FS) FS is one of the most common syndromes associated with congenital diaphragmatic hernia (1.3–10%) and has an incidence of 1/14,000 births [5,6,7]. (15) Fryns syndrome is characterized by diaphragmatic defects (diaphragmatic hernia, eventration, hypoplasia, or agenesis); characteristic facial appearance (coarse facies, wide-set eyes, a wide and depressed nasal bridge with a broad nasal tip, long philtrum, low-set and anomalous ears, tented vermilion of the upper lip, wide mouth, and a small jaw); short distal phalanges of the fingers and toes ...

Based on the provided context, it appears that there are limited treatment options available for Fryns syndrome.

• Currently, there is no specific treatment for Fryns syndrome [7]. Patients require general supportive care and management of associated malformations [2].
• There is no available treatment for the underlying MED12 malfunction in Lujan-Fryns syndrome, which is a related condition to Fryns syndrome [8].
• In some cases, CDH (congenital diaphragmatic hernia) in Fryns syndrome may be amenable to prenatal surgical repair [10].

It's worth noting that the exact cause of Fryns syndrome remains unclear, and there are no specific drugs or therapies available for its treatment.

However, it's also mentioned that patients with seizures associated with Fryns syndrome should avoid epileptogenic drugs (e.g., meperidine/pethidine) or drugs that decrease the seizure threshold [14].

In summary, while there is limited information on drug treatment for Fryns syndrome, it appears that general supportive care and management of associated malformations are the primary approaches.

Fryns syndrome, also known as Fryns dysmorphic syndrome, was a rare genetic disorder characterized by diaphragmatic defects, digital and facial abnormalities, and brain anomalies. However, it appears that the condition has been reclassified or is no longer considered a distinct entity in modern medical literature.

According to search results [8][10], the differential diagnosis for Fryns syndrome included several other conditions such as:

• Donnai-Barrow syndrome
• Matthew-Wood syndrome
• Simpson-Golabi-Behmel syndrome
• Craniofrontonasal syndrome
• Cornelia de Lange syndrome
• Tetrasomy 12p

These conditions share some similar clinical features with Fryns syndrome, and a differential diagnosis would be necessary to rule out these possibilities.

It's worth noting that the genetic basis of Fryns syndrome was not well understood, and only one candidate gene had been identified through whole exome sequencing [15]. The diagnosis of Fryns syndrome was made solely on clinical criteria, which may have contributed to its reclassification or obsolescence in modern medical literature.

In summary, while Fryns syndrome is no longer considered a distinct entity, the differential diagnosis for conditions with similar clinical features remains an important consideration in medical practice.