Symptoms and findings in individuals with PHS may vary greatly in range and severity from patient to patient. Whereas some affected individuals may have only a few characteristic abnormalities, others may have a majority of symptoms and physical features associated with the disorder.
The most common characteristic features of PHS include the presence of Extra fingers and/or toes (polydactyly); fusion (osseous syndactyly) of certain fingers and/or toes (digits); and Improper development (dysplasia) of the nails. In some affected persons, the polydactyly associated with PHS may be characterized by the presence of an extra digit between the third and fourth digits (mesoaxial polydactyly) of the hands and/or feet. Affected individuals may have an extra (supernumerary) digit on the “pinky” (ulnar) side of the hand or the outer (fibular) aspect of the foot (postaxial polydactyly). Many individuals with PHS may also have a condition in which a thin covering blocks the anal opening or the passage that normally connects the anus and the lowest part of the large intestine (rectum) fails to develop (imperforate anus).
According to reports in the medical literature, one of the most significant features of PHS is the presence of a malformation of the hypothalamus (hypothalamic hamartoma), a portion of the brain that coordinates the function of the pituitary gland and that regulates many additional bodily functions. The pituitary gland is the hormone-producing gland at the base of the brain. This is a malformation (and is not a tumor) of the hypothalamus and may cause abnormalities in pituitary function in those who are severely affected. Impaired pituitary function can cause an abnormally small penis (micropenis), low functioning of the thyroid (hypothyroidism), growth hormone deficiency, precious puberty, or more rarely, can cause Diabetes or lack of cortisol production. Seizures are also commonly associated with a hypothalamic hamartoma.
In some infants affected by severe hypothalamic hamartoma, decreased or absent pituitary function (hypopituitarism) may be present at birth. This may lead to low blood sugar (hypoglycemia), abnormal electrolyte levels, and unusually high acid levels in blood and body tissue (metabolic acidosis). Affected individuals may also experience lethargy and an abnormal yellowish discoloration of the skin, mucous membranes, and whites of the eyes (jaundice). Hypopituitarism may result in severe, life-threatening complications without prompt, appropriate treatment. (For more information on hypopituitarism, see the Related Disorders section of this report.)
Infants with PHS may also have distinctive features of the head and facial (craniofacial) area including unusually small ears that are rotated toward the back of the head; a short nose with upturned nostrils (anteverted nares) and a broad or flat nasal bridge; and/or an unusually long vertical groove in the middle of the upper lip (philtrum). Affected individuals may also have an unusually small tongue (microglossia); an abnormal cleft or fissure in the larynx, the organ in the throat that is involved in voice production and that prevents food from entering the airway during swallowing; and abnormal division of the epiglottis (bifid epiglottis), the flap of cartilage in front of the entrance to the larynx.
Some individuals with PHS may have additional abnormalities. These may include the presence of certain teeth at birth (natal teeth), abnormal folds of movement-limiting mucous membrane tissue in the cheek area of the mouth (buccal frenula), abnormally short arms and/or legs (limbs), and/or dislocated hips. In some affected individuals, additional abnormalities may include abnormal development of the lobes of the lungs, absence (agenesis) and/or Improper development (dysplasia) of the kidneys; and/or heart defects that are present at birth (congenital heart defects).
Although most individuals with PHS do not have life-threatening malformations, some affected individuals have an early lethality variant of the disorder. This early lethality is most likely attributable to adrenocortical hormone deficiency caused by the hypothalamic hamartoma or severe airway malformations such as laryngotracheal clefts.