Most of them die before the age of 18 months.
Almost all of the cases were associated with intractable epilepsy and lacked psychomotor development. The prognosis in such patients is poor as per previous studies. This may be because of the fact that patient was in epileptic encephalopathy and was not able to take feeds properly leading on to hypoglycemia. Although hyperglycemia is documented in some studies due to presence of ARX gene on pancreas also, our patient had episodes of hypoglycemia whenever he was taken on breast/spoon feeds and remained normoglycemic on intragastric feeds as well as intravenous fluids. Regarding other features, our patient did not possess any distinctive facial features but has intermittently temperature instability was there which may be because of hypothalamic dysfunction. Similar to the above studies, even testis was not detected in our case and testosterone levels were undetectable. Recently few studies have concluded that hypogonadism in this syndrome is primary hypogonadism because of gonadal agenesis or dysgenesis and hypogonadism in XLAG syndrome might result from both central and gonadal defects. Additionally, it was reported that gonadotropin deficiency might exist due to the brain anomalies, but it would not constitute a major factor for the ambiguous genitalia. It was implied that genital abnormality in the XLAG syndrome was primarily due to defective testis formation (primary testicular hypofunction) and the extent of male sex development might be variable in this syndrome. The cause of the ambiguous genitalia is not well known in the syndrome. Defective neuronal migration during the 12th to 16 th weeks of gestation results in a lack of development of gyri and sulci called as Lissencephaly. XLAG is a rare and severe malformation of the brain cortex with abnormal neuronal migration caused by mutations of the aristaless-related homeobox (ARX) gene, which is expressed in the brain and testes tissues. Posterior fossa structures, bilateral thalami, and basal ganglia were normal. A large interhemispheric cyst was seen in mid posterior interhemispheric region measuring 6.5 × 2.6 × 3.9 cm. There was corpus callosum agenesis with parallel orientation of lateral ventricles. MRI brain showed abnormal gyral pattern with smooth broad gyri suggestive of Lissencephaly pachygyria spectrum. Normal male karyotype (46 XY) was seen on chromosomal analysis (46, XY). Neither uterus nor testis were seen in USG abdomen. Levels of 17 OH progesterone (1.52 ng/ml), TSH (1.52 mIU/L), Cortisol (6.80 mcg/dl) were normal and testosterone was not detectable (0.00 ng/ml). Intermittent episodes of hypothermia were present during the hospital stay.
Patient had hypoglycemia intermittently but seizures persisted even blood sugar levels were normal. Other biochemical investigations like serum electrolytes including ionized calcium, liver, as well as kidney function tests were normal. Sepsis screen was negative in the patient. There were no palpable gonads in bilateral inguinal region. He had a micropenis (5 mm) with a single urethral opening and bilateral cryptorchidism. The baby was hypotonic, lying in semi-flexed posture with poor cry and suck reflex. Anterior Fontanelle was at level, heart and lung sounds were normal and there was no organomegaly. The baby was dull looking and vital signs were normal. On physical examination, the newborn had birth weight of 2.2 kg (small for gestational age), length of 51 cm (50 th percentile), and occipitofrontal circumference of 32 cm (microcephaly). The convulsions were refractory to anticonvulsant drugs such as phenobarbital, phenytoin, and levetiracetam. Baby was having refractory subtle as well as multifocal clonic seizures. Baby was second in order and the first sibling was normal on physical examination with no congenital anomalies. There was no sepsis setting in mother and no history of birth asphyxia in the baby. Antenatal history was normal and the baby was born by normal vaginal delivery. A 4-day-old full-term male newborn presented to pediatrics emergency with history of multiple seizures and poor intake since day 3 of life.