Syndrome of Megalencephaly, Polydactyly, and Polymicrogyria Lacking Frank Hydrocephalus, with Associated MR Imaging Findings: Fig 1.

Abstract

SUMMARY:Megalencephaly, polymicrogyria, polydactyly, and hydrocephalus (MPPH) syndrome has been recently recognized and is very rare. Each case reported so far has demonstrated hydrocephalus to varying degrees. We report an infant with MPPH syndrome, but lacking frank hydrocephalus. The additional finding of an abnormally elongated pituitary infundibulum has not been described in this syndrome and, along with the presence of a regressing cystic cavum septum pellucidum, suggests that chronic underlying hydrocephalus may have been present. Megalencephaly, polymicrogyria, polydactyly, and hydrocephalus (MPPH) syndrome was first described in 2004, with only 9 cases reported so far; hence, the prevalence has not yet been determined.1,2 Hydrocephalus has been considered a mandatory component of this syndrome. [1][2][3][4] We report a patient with macrocephaly, polymicrogyria, and polydactyly, but without overt hydrocephalus. We also report an elongated pituitary infundibulum along with a regressing cystic cavum septum pellucidum (CSP); cystic CSP has been described previously in MPPH, but without reports of regression. 2,5,6 We discuss how to distinguish MPPH from other syndromes presenting with polymicrogyria or megalencephaly. Case ReportA 1-day-old boy was born to a healthy nonconsanguineous family at 39-weeks' gestation. Findings of prenatal sonography had suggested mildly dilated lateral and third ventricles, but with an otherwise unremarkable prenatal follow-up. After initially low Apgar scores but subsequent improvement with bag-mask ventilation, the patient was admitted to the neonatal intensive care unit with normal breathing. On physical examination, he was macrocephalic (head circumference Ͼ3.5 SDs above normal) with normal body length and weight, but with bilateral sixth digits along the ulnar aspects of the hands on plain films ( Fig 1A). He had low-set ears, a high arching palate without cleft or cyst, and esotropia. No hypotonia/hypertonia was present, and deep tendon reflexes were normal. Results of blood biochemistry, cultures, and investigations for metabolic disease were unremarkable. Findings of cytogenetic analysis were unrevealing. Kidney and cardiac ultrasound findings were unremarkable.Cranial sonography was then performed, which suggested subtle lateral ventricular dilation. Thereafter, MR imaging demonstrated diffuse polymicrogyria bilaterally, favoring the posterior frontal lobes and perisylvian regions (Fig 1B, -C). Additional findings included an elongated pituitary infundibulum without other sellar abnormalities.A cystic CSP was present, measuring 1.5-cm maximum transverse diameter (Fig 1C). The myelination pattern appeared normal. There was mild colpocephaly of the lateral ventricles, but without enlargement of the anterior recesses of the third ventricle or of the temporal horns of the lateral ventricles (Fig 1D). The midbrain and corpus callosum appeared normal.At 7 months, the patient developed seizures, which were controlled by medication. An electroencephalogram indicated seizure ac...

Megalencephaly Syndromes and Activating Mutations in the PI3K‐AKT Pathway: MPPH and MCAP

“…[ Mirzaa et al, 2004;Colombani et al, 2006;Garavelli et al, 2007;Tohyama et al, 2007;Pisano et al, 2008;Tore et al, 2009;Verkerk et al, 2010;Osterling et al, 2011;Kariminejad et al, 2012]. As its name indicates, this syndrome is characterized by striking, and most often congenital, MEG, bilateral perisylvian PMG, and a high incidence of hydrocephalus and postaxial polydactyly.…”

Prenatal diagnosis of MPPH syndrome

“…To our knowledge, this is first report of MPPH in the second trimester of pregnancy, supported by additional examinations. The MPPH syndrome is a very rare disorder with only 15 cases reported to date . All but one were diagnosed postnatally ranging from day 1 up to 18 months of age (Table ).…”

“…In MCM syndrome, typical vascular skin abnormalities are present, but these are difficult to detect prenatally. Nine of the 15 reported cases had hydrocephalus, requiring ventriculoperitoneal or ventriculo‐atrial shunting in the early months of postnatal life. The prominent fourth ventricle in this fetus evolved to normal in follow‐up MRI and ultrasound, suggesting an obstruction of the aqueduct as cause of the ventriculomegaly.…”

“…Since the initial report in 2004, a small number of cases of megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus (MPPH) syndrome have been reported with some variability in the extent of features …”

Four-year follow-up of megalencephaly, polymicrogyria, postaxial polydactyly and hydrocephalus (MPPH) syndrome

“…Interestingly, of the children with MPPH that have had hydrocephalus and subsequent surgical intervention, mild to moderate ventricular enlargement and progressive megalencephaly persisted postoperatively 2 9. Tore et al 8 report a child with the core features of MPPH without frank hydrocephalus and with normal psychomotor development at 1 year of age despite findings of diffuse polymicrogyria and a seizure disorder. We report an additional case of MPPH without hydrocephalus, a child who is significantly affected at 4-year follow-up and exemplifies the heterogeneous phenotype of MPPH.…”