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Pitt–Hopkins syndrome should be in the differential diagnosis for males presenting with an ATR‐X phenotype
Author(s) -
Takano K,
Tan WH,
Irons MB,
Jones JR,
Schwartz CE
Publication year - 2011
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.2011.01711.x
Subject(s) - phenotype , genetics , differential diagnosis , medicine , pediatrics , biology , pathology , gene
To the Editor : Pitt–Hopkins syndrome [PTHS (OMIM 6109 54)] is characterized by severe intellectual disability (ID), distinct facial features (a wide mouth, fleshy lips, beaked nose with broad nasal bridge and anteverted nares) and periods of hyperventilation followed by aponea (1–6). PTHS was found to be caused by haploinsufficiency of the transcription factor 4 [TCF4 (OMIM 602272)] in 2007 (1, 2). More than 95% of patients have severe ID and PTHS facial features (7). PTHS has been considered as an important differential diagnosis of well-known developmental disorders such as Angelman syndrome [AS (OMIM 105830)], Rett syndrome (OMIM 312750) and Mowat–Wilson syndrome (OMIM 235730), because some characteristic features of PTHS overlap with these syndromes (1, 2, 8–11). We have also suggested that PTHS be included in the differential diagnosis of X-linked α-thalassemia ID [ATR-X (OMIM 301040)] because one of our patients had been suspected of having ATR-X based on his clinical features of severe ID, open mouth expression, a tented upper lip, a full lower lip, a depressed nasal bridge with anteverted nares and wide-spaced incisors (Fig. 1 in Ref. 12). In follow-up to this observation, we analyzed 79 male patients who were submitted for ATRX testing and had negative findings. A heterozygous frameshift mutation, c.624delC (p.S209Afsx25), was found in one male patient. The patient is a 9-year-old male with severe developmental delay and hypotonia (Fig. 1). His unrelated parents and 7-year-old sister are healthy. There is no family history of developmental delay or neuromuscular disease. The pregnancy was uneventful. He was born by emergency caesarean section at 41 weeks following 4 days of labor induction. His birth weight was 3740 g (50th–75th percentile), birth length was 53 cm (75th–90th percentile CDC growth charts for boys). He required some facial oxygen and antibiotics in the immediate neonatal Fig. 1. Facial features of the patient at the age of 8 years. Note the depressed nasal bridge with anteverted nares, a short philtrum, a wide mouth with an everted upper lip and a full lower lip, wide-spaced teeth with prominent central incisors, lumpy ear helices and upswept frontal hair.