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Pitt-Hopkins syndrome is a rare dysmorphic mental retardation syndrome marked by daytime spells of overbreathing interrupted by apnoea. The dysmorphism consists of a large beaked nose, cup-shaped ears with broad helices, a wide mouth, Cupid's bow upper lip, wide and shallow palate and broad or clubbed fingertips. The four patients described so far have been sporadic and represented both sexes. In addition, a pair of sibs with atypical features has been reported as possible Pitt-Hopkins syndrome cases. We describe two unrelated Pitt-Hopkins syndrome patients in order to further define the phenotype. In addition to severe developmental retardation, hypotonia, postnatal growth retardation, microcephaly, abnormal breathing and characteristic dysmorphic features, both had epilepsy and intestinal problems with severe constipation in one and Hirschsprung disease in the other. Other abnormalities were hypopigmented skin macules in one and high-grade myopia in the other. Both had unusual frontal slow-and-sharp-wave discharges on electroencephalography. Magnetic resonance imaging in both showed a similar hypoplastic corpus callosum with missing rostrum and posterior part of the splenium and bulbous caudate nuclei bulging towards the frontal horns. Chromosomal analysis and subtelomere fluorescence in-situ hybridization studies were normal. No mutations were found in the MECP2 or ZFHX1B genes. Extensive metabolic and mitochondrial screens were normal. The electroencephalography and brain magnetic resonance imaging findings appear to be further diagnostic signs in Pitt-Hopkins syndrome, which is also one of the syndromes associated with Hirschsprung disease.

We report three unrelated patients with hypertrichosis, mild to moderate mental retardation, and dysmorphic facial features including low anterior hairline, thick arched eyebrows, nose with broad tip and columella below alae nasi, short philtrum, thick drooping lower lip and simple posteriorly rotated ears. They also had rough skin with hyperkeratotic plaques. Feet and finger tips were broad. All of them had personality problems like aggressiveness, stubborn temperament or tendency to withdraw. Brain MRI showed thick and short corpus callosum. We believe that these patients represent a new syndrome of unknown aetiology.

The facial photos of 76 aspartylglucosaminuria (AGU) patients, 29 obligate carriers and 78 unrelated controls were evaluated for dysmorphic features to see whether this autosomal recessive lysosomal storage disease includes a dysmorphic facial gestalt in addition to the well-known age-related coarsening of the facies and whether the carrier status of AGU might have an effect on the facial features. A consistent dysmorphic gestalt with hypertelorism, a short and broad nose with round nares, simple often small ears with small or missing lobule and modest folding of helices, thick lips and a square shape of face, was found to be present long before the coarsening begins. Recognition of this pattern of facial features might help in the early diagnosis of AGU. Statistically, puffy eyelids were found to be significantly more frequent in AGU carriers than in controls. These findings support an earlier implication that AGU carrier status might have a slight influence on the phenotype.