SOFT syndrome is a rare, congenital disorder characterized by a distinct set of physical traits. The name is an acronym for Short stature, Onychodysplasia, Facial dysmorphism, and Hypotrichosis, features that are noticeable from birth or early life. As a genetic condition, it stems from a specific DNA alteration, leading to developmental differences that manifest in an individual’s appearance and growth.
Defining Characteristics of SOFT Syndrome
The first defining characteristic is short stature, a form of primordial dwarfism where growth restriction begins before birth. Affected individuals are born smaller than typical newborns and grow at a slower rate. This results in a final adult height that is significantly below the normal range, with a median height of around 132.5 centimeters. The short stature is often disproportionate, with limbs that are unusually short compared to the torso.
Another prominent feature is onychodysplasia, the abnormal development of fingernails and toenails. This can manifest in several ways, with nails appearing small, underdeveloped (hypoplastic), or unusually shaped; in some cases, they may be absent. This condition affects both hands and feet and is a consistent finding among individuals with SOFT syndrome, present from birth.
Facial dysmorphism refers to a collection of distinctive facial features. Individuals often have a triangular and elongated face with a prominent forehead (frontal bossing). Other common features include a small chin, a prominent nose, low-set ears, deep-set eyes, and an increased distance between the eyes (hypertelorism).
Hypotrichosis, the final component of the acronym, describes the presence of sparse or thin hair. This can affect the hair on the scalp as well as the eyebrows and eyelashes, which may be noticeably thin or absent. The degree of hair sparseness can vary among individuals, and a high-pitched voice has also been noted in about half of reported patients.
The Genetic Origins
SOFT syndrome is caused by mutations in the POC1A gene. This gene provides instructions for a protein essential to centrioles, which are organelles that play a part in cell division. When the POC1A gene is mutated, the resulting protein functions improperly, disrupting normal cell division and impacting overall growth from the earliest stages.
The inheritance pattern is autosomal recessive, meaning an individual must inherit two mutated copies of the POC1A gene—one from each parent—to have the syndrome. The parents are carriers, each having one mutated and one normal copy of the gene. Because they have a functional copy, carriers do not show signs or symptoms.
With each pregnancy, two carriers have a 25% chance of having a child affected by SOFT syndrome, a 50% chance of having an unaffected carrier child, and a 25% chance of having a child who is unaffected and not a carrier. This inheritance pattern explains why the syndrome can appear in a family with no prior history of the condition.
Diagnosis and Evaluation
The diagnostic process for SOFT syndrome begins with a thorough clinical evaluation. A physician, often a clinical geneticist or pediatrician, will assess the patient’s physical characteristics. This includes measuring height to confirm short stature, examining the nails for onychodysplasia, observing facial features, and noting hypotrichosis. The presence of all four characteristics strongly suggests the syndrome.
To confirm a clinical suspicion, a definitive diagnosis is achieved through molecular genetic testing. This involves analyzing a blood sample to look for mutations in the POC1A gene. Identifying pathogenic variants in both copies of this gene provides a precise confirmation of SOFT syndrome. This genetic testing also helps differentiate it from other conditions with overlapping features, such as Russell-Silver syndrome or 3M syndrome.
Management and Care
There is no cure for SOFT syndrome, so medical care focuses on managing symptoms and supporting the individual’s quality of life. This requires a coordinated, multidisciplinary team of specialists to address the various aspects of the condition, monitor development, and prevent complications.
The care team may include several specialists. An endocrinologist monitors growth, though recombinant human growth hormone has often been found ineffective. A dermatologist can offer strategies for managing hair and nail problems. A developmental pediatrician tracks physical and cognitive development to address any delays early.
A genetic counselor also plays a role in the management process by providing information and support to the family. They can explain the genetic basis of the syndrome, the inheritance pattern, and what it means for future pregnancies. This comprehensive care, bringing together experts from different fields, helps individuals with SOFT syndrome. Regular monitoring for potential complications, such as insulin resistance, is also a component of long-term care.