Perlman syndrome is a rare congenital overgrowth disorder, characterized by distinctive physical features and an increased risk of specific medical complications. It involves excessive growth before and after delivery. Its rarity means that medical professionals may encounter it infrequently, making awareness of its unique aspects particularly valuable.
Causes and Genetic Basis
Perlman syndrome arises from genetic mutations within the DIS3L2 gene, located on chromosome 2 at position 2q37. These mutations disrupt the normal function of the gene, which is involved in RNA degradation and cell cycle control. The DIS3L2 gene encodes a component of the exosome complex, which regulates RNA processing and degradation.
The inheritance pattern for Perlman syndrome is autosomal recessive. This means an individual must inherit two altered copies of the DIS3L2 gene, one from each parent, to develop the condition. If both parents are carriers, there is a 25% chance with each pregnancy that their child will inherit two altered copies and develop Perlman syndrome.
Key Characteristics and Symptoms
Perlman syndrome manifests both before and after birth with a range of physical and developmental features. Prenatal signs often include polyhydramnios, an excess of amniotic fluid surrounding the fetus, and fetal macrosomia, indicating a larger-than-average size. Ultrasound examinations may also reveal macrocephaly, enlarged kidneys, or cystic hygroma or thickened nuchal translucency during earlier trimesters.
After birth, affected infants present with neonatal macrosomia and muscular hypotonia, leading to a floppy appearance. Distinctive facial features are common, such as a prominent forehead, deep-set eyes, a broad and flat nasal bridge, and an everted V-shaped upper lip. Internal organ enlargement, known as organomegaly, is common, affecting various organs including the kidneys.
A primary concern for individuals with Perlman syndrome is the increased risk of developing a Wilms tumor, a type of kidney cancer. Histological examination of kidneys reveals nephroblastomatosis, which are precursor lesions to Wilms tumor. Other internal issues can include cryptorchidism in males and hyperplasia of the Langerhans cells in the pancreas, which may lead to hyperinsulinism.
Diagnosis and Prenatal Detection
Suspicion of Perlman syndrome may arise during pregnancy through prenatal ultrasound examinations. Observations such as excessive fetal growth, increased amniotic fluid volume, and enlarged kidneys may suggest the syndrome’s presence. These findings prompt further investigation to determine the underlying cause of the fetal abnormalities.
After birth, a diagnosis is suggested by a clinical evaluation of the infant’s characteristic physical features, including their large size, muscle tone, and specific facial characteristics. However, a definitive diagnosis relies on molecular genetic testing. This involves analyzing a blood sample to identify specific mutations in the DIS3L2 gene. Genetic testing can be performed using a multigene panel or more comprehensive exome or genome sequencing.
Management and Health Considerations
There is no specific cure for Perlman syndrome, and management focuses on supportive and symptomatic care to address the various health challenges. A multidisciplinary medical team, including pediatricians, nephrologists, oncologists, and developmental therapists, is involved to provide comprehensive care.
A primary aspect of ongoing care is surveillance for Wilms tumors, given the high risk associated with the syndrome. Regular abdominal ultrasounds are performed to monitor the kidneys for any signs of tumor development. Tumors develop around a mean age of 19 months and can be bilateral, affecting both kidneys. Supportive care also extends to managing feeding difficulties and addressing developmental delays through various therapeutic interventions.
Prognosis and Long-Term Outlook
The long-term outlook for individuals with Perlman syndrome varies, with a high mortality rate during the neonatal period. Renal failure and refractory hypoxemia are common causes of early death. For those who survive infancy, ongoing medical attention is necessary due to persistent health risks.
Individuals who live beyond the first year face a significant risk of developing a Wilms tumor. A majority also experience neurodevelopmental delay, including motor and speech delays, and potential intellectual disability. Early diagnosis and consistent medical surveillance, particularly for Wilms tumors, are important for improving outcomes and managing the syndrome’s progression.