Faciodigitogenital Syndrome, Autosomal Recessive

Clinical Features

Teebi et al. (1988) described an Arabic family with normal consanguineous parents and 5 children (3 males and 2 females) with some features of Aarskog syndrome (see 305400) in addition to unusual hair changes. The hair was coarse, dry, and relatively hypopigmented with widow's peak trait (194000). The hands were small and broad with mild interdigital webbing, fifth finger clinodactyly, and hyperextensible joints. The feet were small with metatarsus varus and stubby toes. Hypertelorism and, in the males, shawl-like scrotum completed the similarities to Aarskog syndrome.

In the same Kuwaiti Bedouin tribe from which the first family came, Teebi and Al Awadi (1991) observed another sibship with 2 affected males who were double first cousins to the first reported cases. Moreover, they observed 3 other distantly related sibships with 9 affected members who all could be traced to a common ancestor. The consistent features were a triangular or elongated face, telecanthus or mild hypertelorism, wide palpebral fissures without ptosis, short stubby nose with anteverted nostrils, high arched and narrow palate, long, deep philtrum, wide mouth with protruding lower lip, posteriorly rotated ears with minor ear anomalies, long neck with sloping shoulders, small, broad hands with mild interdigital webbing and fifth finger clinodactyly, hyperextensible hand joints, and shawl scrotum. Short stature was confirmed in 10 cases, while the heights of the other 6 were between the 10th and 25th percentile for age. None of the 16 cases showed physical disability or mental retardation.

Xu et al. (2010) reported a Chinese family in which 10 of 29 members had a disorder suggestive of Aarskog syndrome but with different limb anomalies and additional features. Characteristic manifestations of Aarskog syndrome included short stature, hypertelorism, long philtrum, and shawl scrotum, and less common manifestations of the syndrome included widow's peak, high-arched palate, abnormal teeth, retarded bone age, 4-finger flexion creases, adducted thumbs, vertebral malformations, pectus excavatum, broad feet with bulbous toes, phimosis, cryptorchidism, and mental retardation. Hyperextension of the proximal interphalangeal joints, one of the most characteristic features in the hands in Aarskog syndrome, was absent, but fifth finger clinodactyly, broad hands with interdigital webbing, and hyperextensible elbows were present. Additional features included central facial paralysis, trismus, hearing impairment, congenital absent 12th ribs, and frequent micturition.

Inheritance

Consanguinity and affected sibs in the families with an Aarskog-like syndrome reported by Teebi et al. (1988) and Teebi and Al Awadi (1991) suggested autosomal recessive inheritance.

In a Chinese family with an Aarskog-like syndrome, Xu et al. (2010) excluded the FGD1 gene (300546), which is mutated in X-linked Aarskog syndrome, as a candidate for the disorder by linkage and sequence analysis. The occurrence of male-to-male transmission suggested autosomal dominant inheritance (see 100050), but autosomal recessive inheritance could not be excluded because affected members were born to consanguineous parents; in addition, because the family originated from a small geographic area, it was possible that seemingly unrelated parents were carriers due to a founder effect.