Fronto-nasal dysplasia or the median cleft face syndrome is characterized by marked hypertelorism in conjunction with a broad nasal tip which is frequently bifid. It is usually sporadic but familial cases have been reported. Bifid nose without hypertelorism has also been reported. Bifid nose can also be a feature of many other syndromes.
Al-Gazali et al. (2002) reported a family, resident of the United Arab Emirates, in which four children were affected with a syndrome of abnormal, bifid nose associated with renal and ano-rectal anomalies. The parents were second cousins of Egyptian origin with a history of one miscarriage at two months of gestation. The first case in the family is for a female child who was noted at birth to have a short nose with depressed bridge and a wide bulbous and cleft tip. Her voice was hoarse and low pitch. Her toes were overlapping. The anus was anteriorly placed. Chromosome analysis and thyroid function tests were normal. Ultrasonography of the kidneys revealed agenesis of the right kidney. At the age of 6 years she was attending school at the appropriate grade for her age. The second case in the family is for a male child who, at birth, had abnormal nose and hoarse low pitch cry. He had a similar nasal appearance to his sister. The anal opening was anteriorly placed and narrow. The toes were overlapping and the fifth toes were short and incurved with small toenails. Renal ultrasonography showed agenesis of the right kidney. The third case in the family is for a female child who, at birth, was noted to have rectal atresia and recto-vaginal fistula. Her voice was noted to be hoarse and low pitch. She had similar dysmorphic features to those of her sibs. Renal ultrasonography revealed absent left kidney. This was confirmed by isotope scanning. The fourth case in the family was for a male child who was the product of a pregnancy complicated by severe oligohydramnios. Prenatal ultrasound revealed bilateral renal agenesis. At birth the baby was noted to have squashed face with abnormal nose similar to his sibs. The baby died after 35 minutes. Al-Gazali et al. (2002) excluded the consideration of Pallister-Hall syndrome as the patients did not show signs of hypothalamic hamartoma or hypopituitarism and the characteristic limb abnormalities. That is why they suggested that the described cases represent a novel autosomal recessive syndrome.
Alazami et al. (2009) followed up on a consanguineous family of an Egyptian origin in which four siblings had bifid nose associated with anorectal and renal abnormalities (BNAR). Only three sibs survived. The deceased sib suffered bilateral renal agenesis, while the surviving three had unilateral renal agenesis, low-pitched crying, short and thick oral frenula, incurved fifth toe, anteriorly placed anus, and stenosis of the anal opening. The bifid nose with bulbous nasal tip was not accompanied by hypertelorism, which makes this case a distinct autosomal-recessive phenotype. The causative mutation was a homozygous single base pair deletion in exon 17 of FREM1 (c.2721delG), which was predicted to cause a frameshift at amino acid 908 and a premature truncation 17 residues downstream (p.V908SfsX17).
[See: Egypt > Al-Gazali et al., 2002; Alazami et al., 2009].