Discussion:
The diagnosis of PHS is usually suspected at a young age based on the association of polydactyly and hypothalamic hamartoma [1,5-9]. However, due to its extreme rarity, the diagnosis may be unrecognized for a long time. Endocrine manifestations can then be in the foreground and reveal the diagnosis as was the case for our patient who presented with an adrenal crisis. Adrenal insufficiency is in most cases linked to a hypothalamic hamartoma which is noted in 90 to 100% of cases of PHS [4,9]. Cases of congenital adrenal hypoplasia have also been reported [8,9]. J G Hall’s review reports two PHS cases of death at birth secondary to adrenal insufficiency [10]. Hypothalamic hamartoma leads to one or more pituitary axes deficiencies. However, corticotropin deficiency seems rare in this syndrome, especially in familial forms [8]. Growth hormone deficiency appears to be the most common pituitary deficiency, but short stature in PHS may also be the result of intrauterine growth retardation [9]. Panhypopituitarism has only been reported in one case [9]. For our patient, it is not clear if pituitary deficiencies were secondary to the hamartoma or to the hypothalamic-pituitary surgery.
It should also be noted that the characteristics of hamartoma in PHS differ from those of non-syndromic hamartomas. Epilepsy, behavioral disturbances and gelastic seizures are less common in PHS and respond better to treatment if they are present [8, 11,12]. Our patient had no history of seizures and had no behavioral disturbances. Precocious puberty can also reveal hamartoma. Its prevalence seems to be less important in hamartomas associated with PHS than in non-syndromic hamartomas [11]. Asymptomatic hamartoma detected incidentally on imaging have also been reported [13]. Thus, hamartomas in PHS usually only require monitoring and surgery is usually not indicated.
The diagnosis of PHS requires screening for associated abnormalities. A bifid epiglottis was found on the otolaryngology examination of our patient. This malformation is present in 40 to 100% of cases in PHS and is most often asymptomatic [8,9,13-15]. However, some patients present with more severe posterior laryngeal clefts, leading to potentially fatal respiratory failure [1,8]. Bifid epiglottis is a rarely isolated birth defect, and its detection should suggest the diagnosis of PHS [14]. Heart, lung, and kidney malformations have also been reported in PHS. Cardiac, abdominal, and renal ultrasound were normal in our patient. Urogenital abnormalities are reported in almost half of cases such as micropenis, hypospadias and uterovaginal aplasia [4, 9]. The micropenis in the present case can be related to the syndrome but can also be explained by congenital hypogonadotropic hypogonadism.
The management in the present case will be limited to hormonal replacement therapy. The delay in the diagnosis and management of growth hormone deficiency has compromised the final height of the patient. An early treatment with growth hormone may have given him normal growth. Galasso et al . described a case of a PHS boy treated from the age of 3 years and for 7 years with growth hormone. His final height was 5.5 cm above his target height [16].