Is this the Coffin–Siris syndrome or the BOD syndrome?

Coffin and Siris [1970] described three unrelated girls with mental impairment and growth restriction associated with the absence of the nail and distal phalanx of the fifth finger. Since then, more than 70 additional patients have been described with similar features. Fleck et al. [2001] presented a comprehensive review of the clinical manifestations of Coffin–Siris syndrome (CSS) and proposed minimal clinical diagnostic criteria [Fleck et al., 2001]. These criteria include developmental delay, coarse facial features, hirsutism, and hypoplastic or absent fifth fingernails or toenails or fifth distal phalanges. Senior [1971] described six children with short stature, tiny dysplastic nails in one or more of the toes bilaterally, short fifth fingers, wide mouth, broad nose, and mild intellectual deficit. Although there was an overlap between the phenotypic findings of the Coffin–Siris and the ‘‘Senior’’ syndromes, some authors have suggested that the latter, which was subsequently called brachymorphism-onychodysplasia-dysphalangism (BOD) syndrome, is a distinct and separate entity [Verloes et al., 1993; Ounap et al., 1998]. The etiologies of the CSS and BOD syndromes are still unknown and in most cases the disorder is sporadic. Both autosomal recessive [Franceschini et al., 1986; Bonioli et al., 1995; Ounap et al., 1998] and autosomal dominant inheritance [Elliott and Teebi, 2000; Flynn and Milunsky, 2006] have been postulated or described. There is evidence pointing towards the 7q32–q34 chromosomal region as being associated with this syndrome. This is based on two CSS case reports that were associated with balanced reciprocal translocations within the long arm of chromosome 7: t(7;22) (q32;q11.2) and t(1;7)(q21.3;q34) [McPherson et al., 1997; McGhee et al., 2000]. In this report, we describe a 7-year-old girl who presented with clinical and physical findings found in patients with CSS and BOD syndrome. The patient exhibited atypical skeletal findings. We compare the clinical presentation of our patient with the previously reported cases and discuss the overlap between CSS and the BOD syndrome that probably represent allelic variants for the same genetic defect. The girl was born at term via spontaneous vaginal delivery to a healthy 35-year-old G2P2 mother and a 45-year-old healthy father, both of Caucasian descent. Her birth weight was 2.72 kg (between 3 and 10th centile) and her length was 45.7 cm (5th centile). The family history is negative for birth defects, mental retardation, infant deaths, consanguinity, or genetic/metabolic disorders. The prenatal history documents no major complications or exposures. During early infancy the patient was diagnosed with torticollis and received occupational therapy for 6 months. She underwent placement of pressure-equalization ear tubes at 10 months of age with significant improvement of recurrent ear infections. During the first year of life, the patient was diagnosed with gastroesophageal reflux, which was controlled with conservative medical treatment. At 1 year of age, an evaluation of a heart murmur revealed a large premium atrial septal defect and a cleft mitral valve that were surgically repaired. At 2 years of age, the patient underwent a surgical repair of bilateral inguinal and umbilical hernias. A complaint of urinary incontinence was evaluated by a cystometrogram that demonstrated bladder irritability at a total bladder capacity of 150 ml, which was considered a slightly smaller than normal capacity for her age. The patient was put on an anticholinergic treatment and showed a remarkable response. At the age of 5 years the patient underwent bilateral medial rectus recession for accommodative esotropia. The patient’s motor skills were normal for her age. She was sitting independently at 6 months and walking at 14 months. She was slightly slow to say her first words, but was pointing to show things by 18 months and putting two words together by 2 years. The patient was toilet trained only at the age of 5 years when she was put on anti-cholinergic medication for bladder incontinence. A formal developmental evaluation at the age of 7 years and 3 months demonstrated low to middle first grade level skills in math and reading with some visual fine motor problems. A speech and language evaluation revealed a moderate articulation disorder, but